The methanol extract of Amaranthus spinosus L. leaves was evaluated for anti-inflammatory activities in different animal models. The effect of the plant extract was also studied on castor oil-induced diarrhea and gastric mucosal integrity. The extract (25-100 mg/kg) inhibited the carrageenan-induced rat paw edema and produced significant (p < 0.05) inhibition of acetic acid-induced increased vascular permeability. Inhibition of the cotton pellet granuloma was also inhibited by 100 mg/kg of the plant extract. Analgesic activity was exhibited with the significant and dose-related reduction in the number of writhings induced with acetic acid, as well reduction in paw licking induced by injection of formalin in mice. The extract (50 and 100 mg/kg) produced gastric erosion in rats, following repeated administration for 4 days, and with 25-100 mg/kg of the extract, there was a statistically significant (p < 0.05) reduction in castor oil-induced diarrhea in rats. These results demonstrate the anti-inflammatory properties of the leaf extract of A. spinosus. It is also suggested that the plant extract probably acts by the inhibition of prostaglandin biosynthesis.