Inflammation underlies many pathological conditions and remains a major therapeutic target. Despite the efficacy of synthetic antiinflammatory drugs, their side effects have prompted a renewed interest in medicinal plants with traditional uses. Laportea aestuans has been used in African ethnomedicine for treating inflammationrelated disorders. This study identified the active principles and evaluated the antiinflammatory property of ethanol leaf extracts of Laportea aestuans in animal models. Leaves were extracted using 90% ethanol in maceration method. The phytochemical screening was performed using Trease and Evans method (2002). The acute toxicity studies was carried out with Lorke’s method (1983). Acute inflammation was induced in Swiss mice using carrageenan-induced paw edema and formalin-induced inflammation models. The extract was administered at 100, 200, and 400 mg/kg orally, and compared to standard drug; aspirin (10 mg/kg). The paw volumes were measured at 0, 1, 2, 3, and 4 hours post-induction. Results were analyzed using one-way ANOVA, mean and standard deviation taking P<0.05 to be significant. The ethanol leaf extracts of Laportea aestuans contained phenolic compound, alkaloids, flavonoids, tannins, and saponins, terpenoids and steroids. It significantly (p<0.05) inhibited paw edema in a dosedependent manner in both models. Maximum inhibition was observed at 400 mg/kg, comparable to the standard drug; aspirin. Ethanol leaf extracts of L. aestuans possesses significant anti-inflammatory property, orchestrated by phytochemicals such as flavonoids and alkaloids, and therefore, validated its traditional use and suggested novel anti-inflammatory agent for development.