Leishmania amazonensis is one of the major etiological agents of diffuse cutaneous leishmaniasis, which is frequently unresponsive to all known treatments. Syagrus coronata (Arecaceae) is a palm tree with industrial applications used in local medicine by the Brazilian ?caatinga? communities. This work evaluates the in vitro leishmanicidal activity of S. coronata on L. amazonensis. Promastigote forms of L. amazonensis were treated with different concentrations of the aqueous extract from S. coronata. In addition, we evaluated the effect of the aqueous extract on infection of mouse peritoneal macrophages and nitric oxide production. The minimal inhibitory concentration (MIC) of the aqueous extract of S. coronata was 8.3 µg/ml. Morphological changes in L. amazonensis promastigotes treated with 50 µg/ml of the aqueous extract were observed by light microscopy. Pretreatment of mouse peritoneal macrophages with 33 µg/ml of S. coronata aqueous extract reduced the association index between macrophages and L. amazonensis by 70.4%, with a concomitant increase of 158.3% in nitric oxide production by the infected macrophages. In addition, the aqueous extract exhibited no cytotoxic effect on mammalian cells and elicited no allergic reactions in vivo, indicating good prospects for the development of new drugs of herbal origins to treat leishmaniasis