Pharmacological investigations were carried out with aqueous methanolic extract (AME) ofSwietenia mahagoni (L.) Jacq. (Meliaceae) leaves. Acute toxicity studies revealed that the LD50 doseof AME was 600 mg/kg, i.p. AME was found to possess significant anti-inflammatory activity inacute, sub-chronic and chronic models of inflammation. AME selectively inhibited cyclooxygenase(COX)-2 activity, which is involved in arachidonic acid metabolism and biosynthesis ofprostaglandins under inflammatory conditions. Treatment with AME significantly enhanced totalperitoneal cell count and the number of macrophages in normal mice, which revealed that AMEmay also alter the immune response along with its anti-inflammatory effect. The saponins or thealkaloids present in AME may be responsible for the anti-inflammatory activity.