Background: According to the drug resistance and side effects of the standard treatments for leishmaniasis, achieving effective treatment with less side effects and more benefits is of paramount importance. The present study aimed to evaluate the effect of Aloe vera leaf exudate on Leishmania major under in vitro and in vivo models, in inbred BALB/c mice. Methods: Different concentrations of both Aloe vera leaf exudates (AVL) and the standard drug meglumine antimoniate (Glucantime®;Sanofi-Aventis, France) were prepared (9.375l, 18.75, 37.5, 75, 150, and 300 ?g/ml) for in vitro model and then were applied to the fixed number of promastigotes. The promastigotes were counted after 24, 48, and 72 h. The viability of promastigotes was tested by MTT. A total of 20 mice with cutaneous leishmaniasis were divided into four groups for in vivo model, 1: positive group (treatment with Glucantime®), 2: negative group (without treatment), and 3 and 4: experimental groups (treatment with AVL1% and AVL4%, respectively). The size of the ulcers were recorded at the beginning of the experiment on a weekly basis for four weeks. Results: The results of in vitro model indicated that both AVL and Glucantime® reduced the number of promastigotes such that there was the lowest number of parasites in the concentration 300 ?g/ml of AVL and Glucantime®; however, the difference between them was not statistically significant. In vivo model demonstrated that AVL4% and Glucantime® decreased significantly the size of ulcers more than negative (P=0.000) and AVL1% groups (P=0.000 and P=0.004, respectively). Conclusions: There was no significant difference between AVL4% and Glucantime® (P=0.634). Therefore, AVL could control the Leishmania major.