There is a great tendency toward the consumption of traditional plants in the cases of leishmaniases. The aim of this study was to evaluate the leishmanicidal effects of different extracts of Euphorbia microsciadia Bioss on promastigotes of Leishmania major in vitro. Arterial parts of the plant were dried and extracted with methanol or macerated in ethanol. Five different concentrations of each extract (1, 0.5, 0.25, 0.125, 0.0625 mg.mL-1), amphotericin B (0.5 mg.mL-1) (positive control) and culture medium (negative control) were placed in 24-well plates containing 40,000 parasites/well. The plates were incubated for six consecutive days at 25°C and the number of the parasites in each well was determined microscopically on the days 2, 4 and 6 of the experimental procedure. Amphotericin B at the specified concentration killed all the parasites. A concentration-dependent lethal toxicity was observed for different doses of the extracts. Exposure of promastigotes to 1 mg.mL-1 of both extracts exhibited the most leishmanicidal activity. The EC50 values for the methanol (Soxhlet) and ethanol (macerated) extracts were determined (0.078 - 0.331 mg.mL-1) four days after incubation. Our results indicate that both extracts of E. microsciadia Bioss exhibit favorable lethal toxicity against promastigote of L. major and may be suitable candidates for further research in future leishmanicidal studies.