The present study focuses on the anti-inflammatory activity of Justicia gendarussa Burm.f. on an acute model of inflammation: the carrageenan-induced paw edema assay. Methanolic extract of J. gendarussa (JRM) roots at a dose of 100 mg/kg significantly inhibited edema formation 5 h after carrageenan induction. JRM inhibited carrageenan-elicited total cycloxygenase activity, 5-lipoxygenase and 15-lipoxygenase activities in blood mononuclear cells of rats, decreased neutrophil infiltration in paw tissue as shown by low myeloperoxidase activity, and also caused a 53% inhibition in cyclooxygenase-2 activity in paw tissue. Purification of JRM by liquid-liquid partitioning yielded an ethyl acetate fraction of JRM that showed interleukin-6 downregulation potential and the ability to inhibit prostaglandin E2 production in vivo. The present investigation provides pharmacological evidence to support the folklore claim that J. gendarussa is an anti-inflammatory agent.