Background and Objective: Vitamin C (Vit.C) or ascorbic acid is an essential micronutrient which has neuroprotective effects and can decrease Cyclooxygenase-2 (COX-2) activity and then prostaglandins synthesis. Therefore, it is hypothesized that Vit. C is able to reduce the inflammatory edema. In order to verify this hypothesis, a model of inflammatory paw edema was induced by formalin in rats. Materials and Methods: 56 Male Wistar rats (200-250g) were used to carry out this study. Each group consisted of 7 mice, composed of Saline (intraperitoneal IP), Saline (intrathecal IT), Vit.C at the dose groups of (1, 10, 100, 200 mg/kg, IP) and concentration of (0.02mg/10µl, IT) in normal and neutralized forms of Vit.C. 30 minutes after IP and 5 minutes after IT administrations, 0.05ml formalin 2.5% was injected in the sub plantar region of left hind paw. Volume of edema was measured by subtraction of paw volume assessed using plethysmometric method before the injections, from the paw volume 1 hour after formalin injection. Results: IP administration of Vit.C at doses of 200 mg/kg (P<0.05), 100 mg/kg (P<0.001) and 10 mg/kg (P<0.01) and also intrathecal administration of both normal and neutralized forms of Vit. C (0.02 mg/10µl) (P<0.001) significantly reduced the inflammatory paw edema. Conclusion: Effects of Vit.C on inflammatory edema reduction was significant. The effects of Vit.C are probably dose dependent and acidic independent. References 1- Helmersson J, Arnlöv J, Larsson A, Basu S. Low dietary intake of beta-carotene, alpha-tocopherol and ascorbic acid is associated with increased inflammatory and oxidative stress status in a Swedish cohort. Br J Nutr. 2009 101: 1775-82. 2- Skaper S, Fabris M, Ferrari V, Dalle Carbonare M, Leon A. Quercetin protects cutaneous tissue-associated cell types including sensory neurons from oxidative stress induced by glutathione depletion: cooperative effects of ascorbic acid. Free Radic Biol Med. 1997 22: 669-78. 3- Pauling L. Evolution and the need for ascorbic acid. Proc Natl Acad Sci U S A. 1970 67: 1643-8. 4- Williams R, Paterson C. A protective role for ascorbic acid during inflammatory episodes in the eye. Exp Eye Res. 1986 42: 211-8. 5- Suh M, Kwon J, Wee W, Han Y, Kim J, Lee J. Protective effect of ascorbic acid against corneal damage by ultraviolet B irradiation: a pilot study. Cornea. 2008 27: 916-22. 6- Clemetson C. Histamine and ascorbic acid in human blood. J Nutr. 1980 110: 662-8. 7- Candelario-Jalil E, Akundi R, Bhatia H, et al. Ascorbic acid enhances the inhibitory effect of aspirin on neuronal cyclooxygenase-2-mediated prostaglandin E2 production. J Neuroimmunol. 2006 174: 39-51. 8- Spillert C, Spillert K, Hollinshead M, Lazaro E. Inhibitory effect of high dose ascorbic acid on inflammatory edema. Agents Actions. 1989 27: 401-2. 9- Gunes T, Bozok S, Kestelli M, et al. α-tocopherol and ascorbic acid in early postoperative period of cardiopulmonary bypass. J Cardiovasc Med (Hagerstown). 2012 13: 691-9. 10- Olatunji-Bello II, Olayemi SO, Daramola AO, Ogungbemi AO. Ascorbic acid and the effect of cigarette smoke on tissues--a preliminary report. West Afr J Med. 2008 27: 78-81. 11- Silva Bezerra F, Valença S, Lanzetti M, et al. Alpha-tocopherol and ascorbic acid supplementation reduced acute lung inflammatory response by cigarette smoke in mouse. Nutrition. 2006 22: 1192-201. 12- Dai F, Yang J, Gu P, Hou Y, Wu C. Effect of drug-induced ascorbic acid release in the striatum and the nucleus accumbens in hippocampus-lesioned rats. Brain Res. 2006 1125: 163-70. 13- Tillement JP, Albengres E. The pharmacologic basis of pain treatment. Therapie. 2001 56: 687-96. 14- Zimmermann M. Ethical considerations in relation to pain in animal experimentation. Acta Physiol Scand Suppl. 1986 554: 221-33. 15- De Vito M, Wagner G. Methamphetamine-induced neuronal damage: a possible role for free radicals. Neuropharmacology. 1989 28: 1145-50. 16- Heller R, Unbehaun A, Schellenberg B, Mayer B, Werner-Felmayer G, Werner ER. L-ascorbic acid potentiates endothelial nitric oxide synthesis via a chemical stabilization of tetrahydrobiopterin. J Biol Chem. 200 276: 40-7. 17- Yaksh T, Rudy T. Chronic catheterization of the spinal subarachnoid space. Physiol Behav. 1976 17: 1031-6. 18- Roche AK, Cook M, Wilcox GL, Kajander KC. A nitric oxide synthesis inhibitor (L-NAME) reduces licking behavior and Fos-labeling in the spinal cord of rats during formalin-induced inflammation. Pain. 1996 66: 331-41. 19- Fereidoni M, Ahmadiani A, Semnanian S, Javan M. An accurate and simple method for measurement of paw edema. J Pharmacol Toxicol Methods. 2000 43: 11-4. 20- Dray A. Inflammatory mediators of pain. Br J Anaesth. 1995 75: 125-31. 21- Medzhitov R, Horng T. Transcriptional control of the inflammatory response. Nat Rev Immunol. 2009 9:92-703. 22- Peponis V, Papathanasiou M, Kapranou A, et al. Protective role of oral antioxidant supplementation in ocular surface of diabetic patients. Br J Ophthalmol. 2002 86: 1369-73. 23- Rosa K, Gadotti V, Rosa A, Rodrigues A, Calixto J, Santos A. Evidence for the involvement of glutamatergic system in the antinociceptive effect of ascorbic acid. Neurosci Lett. 2005 381: 185-8. 24- Kim E, Won R, Sohn J,et al. Anti-oxidant effect of ascorbic and dehydroascorbic acids in hippocampal slice culture. Biochem Biophys Res Commun. 2008 366: 8-14. 25- Garland DL. Ascorbic acid and the eye. Am J Clin Nutr. 1991 54: 1198S-1202S. 26- Maghbooli M, Farhadi S, Esmaeelzadeh A, Mazloomzadeh S. Assessment of serum uric acid and vitamin C levels in acute atherothrombotic stroke. J Zanjan Univ Med Sci. 2012 20: 64-74.