The hexane extract and two sesquiterpenic compounds, cacalol and cacalone, were isolated from the roots and rhizomes of Psacalium decompositum. Then, their anti-inflammatory activity was evaluated in carrageenan-induced rat paw edema and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema. Indomethacin was used as the anti-inflammatory agent of reference. In the rat paw model of inflammation, both the hexane extract and the sesquiterpenes isolated from Psacalium decompositum showed a clear dose-dependent inhibition of the carrageenan-induced edema (P < 0.05), with important differences among them during the temporal course of the inhibition. In the TPA-induced mouse ear edema all tested compounds showed anti-inflammatory activity in dose-dependent manner (P < 0.05). In both models, cacalone showed the most prominent anti-inflammatory activity. We conclude that some of the beneficial effects attributed to Psacalium decompositum in traditional medicine can be related with the anti-inflammatory activity of cacalol and cacalone.