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. 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