A methanol extract of the stem bark of Chlorophora excelsa (Welw.) Benth and Hook was evaluated for anti-inflammatory activity in different models. Acute inflammatory effects were studied in the carrageenan-induced rat paw edema, and the effect of the extract in chronic inflammation was evaluated using the cotton pellet granuloma test. The effect of the extract on topical inflammation induced with croton oil was also tested in mice. The extract produced a significant (p. < 0.05) and dose-dependent inhibition of the carrageenan-induced pedal edema, as well as granuloma tissue formation in rats. Topical anti-inflammatory effect was only evident with 400 mg/kg of the extract. This study demonstrated acute, chronic, and topical anti-inflammatory properties of the methanol extract of C. excelsa.