Objective:In the present study,we evaluated the effects of the aqueous extract of Physalis angulata root (AEPa) on Leishmania infantum proliferation,morphology,and the driving mechanism in leishmanicidal activity and modulatory action on macrophages.Methods:L.infantum promastigotes were treated with 50 and 100 μg/mL AEPa for 72 h and then antipromastigote assay was performed by counts in a Newbauer chamber,morphological changes were analyzed by transmission electron microscopy and the mechanism of the leishmanicidal activity was detected.in addition,macrophages were infected with L.infantum and were used to evaluate anti-amastigote activity of AEPa and effects of AEPa on cytokine secretion after 72-hour treatment.Results:Treatment with AEPa reduced the numbers of L.infantum promastigotes (50％ inhibitory concentration (IC50)=65.9 μg/mL;selectivity index (Sl)=22.1) and amastigotes (ICso =37.9 μg/mL;SI =38.5) compared with the untreated control.Amphotericin B reduced 100％ of the promastigote numbers after 72 h of treatment (IC50 =0.2 μg/mL).AEPa induced several morphological changes and increased the production of reactive oxygen species and apoptotic death in promastigotes after treating for 72 h.AEPa (100 μg/mL) promoted tumor necrosis factor-α secretion in macrophages infected with L.infantum after 72 h of treatment,but did not induce an increase in this cytokine in noninfected macrophages,In addition,AEPa showed no cytotoxic effect on J774-A1 cells (50％ cytotoxic concentration ＞1000 μg/mL).Conclusion:AEPa presented antileishmanial activity against the promastigotes and amastigotes of L.infantum without macrophage cytotoxicity;these results show that natural products such as P.angulata have leishmanicidal potential and in the future may be an altative treatment for leishmaniasis.