Abstract: In this study, the leishmanicidal effect of different extract of Euphorbia bungei Boiss aerial part was evaluated on promastigotes of Leishmania major in vitro. Therefore, dried and ground aerial part of the plant was extracted using either maceration in 80% ethanol or Soxhlet in methanol. Then, 5 different concentrations of each extract, one positive control, one negative control and one solvent control were prepared and were placed in a 24-well plate containing 40,000 parasites/well. The extract concentrations were 0.06, 0.12, 0.25, 0.5 and 1 mg mL-1. Amphotricin B (0.5 mg mL-1) was used as positive control while negative control contained only culture medium. The plate was incubated at 25oC for six days and the amount of parasites in each well was determined on days 2, 4 and 6 of experiment microscopically using Neubar chamber. It was observed that amphotricin B and both macerated and soxhlet extracts at concentration of 1 mg mL-1 killed all parasites. Lower doses exhibited a dose-dependent leishmanicidal activity. The EC50 for macerated and soxhlet extracts in DMSO was between 0.5 and 0.25 mg mL-1. The control solvents had no significant effect on the L. major promastigotes. These results indicated that both macerated and soxhlet extracts of E. bungei Boiss have favorable leishmanicidal activity.