Objective: This study was designed to evaluate the anti-inflammatory and antipyretic activity of ethyl acetate extract of Vitex leucoxylon Linn. in various animal experimental models. Materials and Methods: Ethyl acetate extract of V. leucoxylon Linn. evaluated for anti-inflammatory activity in carrageenan, mediator-induced rat paw edema, and cotton pellet-induced granuloma model. The antipyretic activity was evaluated by yeast-induced pyrexia model. Results: Single administration of the ethyl acetate extract of V. leucoxylon Linn. at dose of 500 mg/kg p.o. showed significant (P < 0.001) inhibition of rat paw edema. The ethyl acetate extract showed significant antipyretic activity in brewer yeast-induced pyrexia in rats throughout the observation period of 4 h. Conclusion: This study shows that ethyl acetate extract of V. leucoxylon Linn. has significant anti-inflammatory and antipyretic activity.