Heliopsis longipes (A. Gray) Blake (Asteraceae) is a species broadly used in Mexican Traditional Medicine. The present study illustrates the effects of the root ethanolic extract from this species on the production of tumor necrosis factor alpha (TNF alpha) and nitric oxide (NO) by activated RAW264.7 macrophage. The extract showed an inhibitory activity on TNF alpha (IC50 = 223.0 mu g/mL) and NO (IC50 = 136.9 mu g/mL). These results represent a contribution to the elucidation of the mechanism involved in the analgesic and anti-inflammatory effects reported for the H. longipes extract.