The presence of inflammation is one of the key factors in the onset and progression of various medical disorders and diseases, making it a crucial challenge for treatment. The purpose of this study is to evaluate antioxidant and anti-inflammatory effects of Vinpocetine, using acute models of inflammation; Xylene-, Carrageenan (CGN)-induced inflammation and acetic acid-induced vascular- permeability in mice were used. We also employed molecular docking approach to verify the underlying mechanism of anti-inflammatory activity of Vinpocetine. In a current investigation, Vinpocetine showed anti-inflammatory and antioxidant effects on Xylene- and CGN-induced inflammation in a dose-dependent manner. Vinpocetine reduced inflammatory edema and restored antioxidant tissue balance, probably via suppression of IL-1β, IL-6, TNF-α, MDA and MPO activity, and also through increased non-enzymatic antioxidant (GSH) levels in paw tissue. Histopathological examination showed that Vinpocetine restored normal skin architecture with significant inhibition of tissue edema, congestion, and cellular infiltration in CGN-challenged paw. Mechanistically, Vinpocetine showed downregulation the expression of COX-2 protein, in western blot assessment, that was associated with significant decrease in the level of prostaglandin E 2 (PGE2) levels; a major metabolic product of COX-2 enzyme. Interestingly, Silico study showed that Vinpocetine has strong affinity to COX-2, similar to diclofenac, suggested possible mechanism of downregulation of COX-2 expression. Therefore, Vinpocetine showed antioxidant and anti-inflammatory responses might, in part, due to inhibition of COX-2/PGE 2 pathway.