Background and Objectives: Diabetes mellitus (DM) especially type2 is one of the main causes of morbidity in developing countries such as Iran. Recently, fenugreek seeds as medical plant have been considered for treatment of diabetes. Therefore, we conducted this study to evaluate the effects of fenugreek seeds on serum metabolic factors and ICAM-1 levels in type 2 diabetic patients. Materials and Methods: This triple-blind randomized controlled clinical trial was conducted on 88 T2DM patients. Subjects in fenugreek seeds (n=44) and placebo (n=44) groups consumed 10 g/d of powdered whole fenugreek seeds or 5 g/d of wheat starch before two meals for 8 weeks. Anthropometric measurements, dietary records and fasting blood samples were collected at the baseline and at the end of the trial. Results: BMI, energy and protein intake were significantly different between placebo and intervention groups at the beginning of the study. Fenugreek seeds significantly decreased fasting blood glucose (P=0.007), HbA1c (P=0.0001), serum levels of insulin (P=0.03), and homeostatic model assessment for insulin resistance (P=0.004) in trial group compared to the placebo group. No significant changes was seen in ICAM-1 levels (P=0.64). Conclusion: Fenugreek seeds improved glucose metabolism. There was no significant difference in ICAM-1 levels in our intervention, regarding dose and time. It seems that fenugreek seeds may be useful in controlling blood glucose and its complications in type 2 diabetic patients. References 1- Medical nutrition therapy for diabetes mellitus and hyperglycemia of nondiabetic origin. In: Mahan LK, Escott-Stump S. Krause's food and nutrition therapy Missouri: Saunders Elsevier. Diabetes Review. 2008: 768-804. 2- Harati H, Hadaegh F, Saadat N, Azizi F. Population-based incidence of type 2 diabetes and its associated risk factors: results from a six-year cohort study in Iran. BMC Public Health. 2009 9: 186. 3- Eidi AEM, Sokhteh M. Effect of fenugreek (Trigonella foenum-graecum. L) seeds on serum parameters in normal and streptozotocin-induced diabetic rats. Nutrition Research. 2007 27: 728-33. 4- Kriketos AD GJ, Peake PW, et al. Inflammation, insulin resistance, and adiposity a study of first-degree relatives of type 2 diabetic subjects. Diabetes Care. 2004 27: 2033-40. 5- Jaleel F, Aftab J, Rahman MA. Relationship between adiponectin, glycemic control and blood lipids in diabetic type 2 postmenopausal women with and without complication of ischemic heart disease. Clinica Chimica Acta. 2006 370: 76-81. 6- Yoshizawa M, Ohsawa K, Ohta M, et al. Elevated serum levels of soluble vascular cell adhesion molecule-1 in NIDDM patients with proliferative diabetic retinopathy. Diabetes Res Clin Pract. 1998 42: 65-70. 7- Weigert J NM, Wanningera J, Wurma S, et al. Reduced response to adiponectin and lower abundance of adiponectin receptor proteins in type 2 diabetic monocytes. FEBS Letters. 2008 582: 1777-82. 8- Luc GAD, Evans A, Amouyel PH, et al. Circulating soluble adhesion molecules ICAM-1 and VCAM-1 and incident coronary heart disease: t prime study. Atherosclerosis. 2003 170: 169-76. 9- Lenghel AR KI, Bondor CI, Rusu C, Rahaian R, Caprioara GM. Intercellular adhesion molecule, plasma adiponectin and albuminuria in type 2 diabetic patients. Diabetes Res Clin Pract. 2012 95: 55-61. 10- Srichamroen A, Field CA, Basu TK. In vitro intestinal glucose uptake is inhibited by galactomannan from Canadian fenugreek seed (Trigonella foenum graecum. L) genetically lean and obese rats. Nutrition Research. 2009 29: 49-54. 11- Srichamroen A, Field CA, Basu TK. The modifying effects of galactomannan from Canadian-grown fenugreek (Trigonella foenum-graecum L.) on the glycemic and lipidemic status in rats. J Clin Biochem Nutr. 2008 43: 167-74. 12- Chatterjee S, Sharma A. Bioactive lipid constituents of fenugreek. Food Chemistry. 2010 119: 349-53. 13- Sharma RD RT. Hypoglycaemic effect of fenugreek seeds in non-insulin dependent diabetic subjects. Nutrition research. 1990 10: 731-9. 14- Kassaian N, Forghani B, Amini M. Effect of fenugreek seeds on blood glucose and lipid profiles in type 2 diabetic patients. Int J Vitam Nutr Res. 2009 79: 9-34. 15- Mandegary A, Sharififar F, Pournourmohammadi SH, Reza Fardiar R, Shooli S. Alkaloid and flavonoid rich fractions of fenugreek seeds (Trigonella foenum-graecum L.) with antinociceptive and anti-inflammatory effects. Food Chem Toxicol. 2012 50: 2503-7. 16- Tribolo S LF, Connor C, Suri S, et al. Comparative effects of quercetin and its predominant human metabolites on adhesion molecule expression in activated human vascular endothelial cells. Atherosclerosis. 2007 197: 50-6. 17- Pourghassem Gargari B, Aliasgharzadeh A, Asghari Jafar-abadi M. Effects of high performance inulin supplementation on glycemic control and antioxidant status in women with type 2 diabetes. Diabetes Metab J. 2013 37: 140-8. 18- Sharma RD. Effect of fenugreek seeds and leaves on blood glucose and serum insulin responses in human subjects. Nutr Res. 1986 6: 64-1353. 19- Tushar K, Kishalay J, Debidas Gh. Protective Effect of aqueous extract of seed of Psoralea corylifolia (Somraji) and seed of Trigonella foenum-graecum L. (Methi) in streptozotocin-induced diabetic rat: a comparative evaluation. Pharmacognosy. 2013 5: 277-85. 20- Puri D, Prabhu KM. Antidiabetic effect of GII compound purified from fenugreek (Trigonella foenum graecum L) seeds in diabetic rabbits. Ind J Clin Biochem. 2012 27: 21-7. 21- Jaiswal N MC, Venkateswarlu K, Sukanya P, Srivastava AK, Narender T, Tamrakar AK. Hydroxyisoleucine stimulates glucose uptake by increasing surface GLUT4 level in skeletal muscle cells via phosphatidylinositol-3-kinase-dependent pathway. Eur J Nutr. 2012 51: 8-893. 22- Atkinson BJ GB, King CD, Josey MA, Olson AL. Moderate GLUT4 overexpression improves insulin sensitivity and fasting triglyceridemia in high-fat diet-fed transgenic mice. Diabetes Metab J. 2013 62: 58-2249. 23- Ogawa J KT, Smirnov SV, Hibi M, et al. A novel L-isoleucine metabolism in Bacillus thuringiensis generating (2S,3R,4S)-4-hydroxyisoleucine, a potential insulinotropic and anti-obesity amino acid. Appl Microbiol Biotechnol. 2010 89: 38-1929. 24- Mohamad S TA, Bamezaia RNK, Basir SF, Baquera NZ. Lower doses of vanadate in combination with trigonella restore altered carbohydrate metabolism and antioxidant status in alloxan-diabetic rats. Clinica Chimica Acta. 2004 342: 105-14. 25- Hamden K MK, Amri Z, Aloulou A, Elfeki A. Inhibition of key digestive enzymes related to diabetes and hyperlipidemia and protection of liver-kidney functions by trigonelline in diabetic rats. Sci Pharm. 2012 81: 46-233. 26- Kannappan S AC. Insulin sensitizing actions of fenugreek seed polyphenols, quercetin & metformin in a rat model. Indian J Med Res. 2009 129: 401-8. 27- Wein S BN, Petersen RK, Kristiansen K, Wolffram S. Quercetin enhances adiponectin secretion by a PPAR-independent mechanism. Eur J Pharm Sci. 2010 41: 16-22. 28- Setorki M, Rafieian M, Heidarian E, et al. The beneficial effects of Vaccinium Myrtilus L. intake on atherosclerosis risk factors in mal new zealand rabbitse. J Zanjan Univ Med Sci. 2012 20: 79. 29- Yamagata K MA, Matsufuji H,Chino M. Dietary flavonoid apigenin inhibits high glucose and tumor necrosis factor α-induced adhesion molecule expression in human endothelial cells. J Nutr Biochem. 2010 21: 116-24.