Background an objective: Leishmaniasis is a common disease endemic in some parts of Iran. Chemical or physical treatments or a combination of both are used for treatment of the disease. Nitric oxide (NO) is important for healing of leishmaniasis in human and animal. This study was designed to evaluate the beneficial effects of a NO releasing cream on cutaneous leishmaniasis in an animal model. Materials and Methods: Balb/c mice were infected with leishmania major by injecting promastigotes into the base of tails of mice to induce the lesion. Then the animals were divided into 3 groups (Control, placebo and treatment). Mice were treated with the drugs one time daily. The diameter of lesions were measured on days 0, 5, 10, 15, 20, 25, and 30 after the appearance of the lesions. Data were analyzed using one-way ANOVA test and (P<0.05) considered as significant. Results: The diameter of lesions were significantly reduced in 15, 20, 25 and 30 day in NO cream treated animals compared to control and placebo groups (P<0.05). Conclusion: NO releasing compounds may be effective in the treatment of leishmaniasis.