Background and Objective: Dietary carbohydrate restriction is one of the most effective approaches in the management of metabolic syndrome. However, there is little information available on the role of inflammatory processes. Materials and Methods: In a randomized cross-over clinical trial, thirty overweight or obese (BMI>25 kg/m2) women with metabolic syndrome were randomly allocated into two groups, to follow either a high-carbohydrate (HC) (60-65% carbohydrates, 20-25% fats) or a moderately-restricted carbohydrate (MRC) (43-47% carbohydrate, 36-40% fats) diet for 6 weeks. After a 2-week washout period, individuals were switched to the alternate diet for an additional 6 week period. At the beginning and the bend of each period, markers of inflammation (hs-CRP, hs IL-6, hs TNF-α and SAA), endothelial function (E-selectin, sICAM-1 and sVCAM-1), and adipocytokines (leptin and adiponectin) were measured in both study groups at baselines (i.e., fasting state). Results: Consumption of the HC diet was associated with increased levels of SAA (3.27 ±1.22 μg/ml), while consumption of MRC diet did not result in such unfavorable effects (P=0.04). Serum concentrations of leptin and adiponectin were reduced by the HC diet (P<0.02), but these changes were not significant between the two diets (P>0.05). Serum concentrations of hs-CRP, hs TNF-α and IL-6 were not influenced by either diet. There were also no significant differences observed between the two diets in terms of their effects on serum sICAM-1, sVCAM-1, and E-selectin concentrations. Conclusion: Short-term substitution of dietary carbohydrates by unsaturated fats seems to have no significant effects on serum levels of adipocytokines, biomarkers of inflammation, and endothelial function except for SAA.