Background: Cutaneous leishmaniasis is an important skin parasitic disease. Ideal treatment is not found yet and seeking for proper drugs continues. Objective: Comparison of the efficacy of fluconazole with systemic glucantime in patients with acute cutaneous leishmaniasis in Ghaem hospital in Mashhad in 2002. Patients and Methods: During one year of study, all patients with cutaneous leishmaniasis were divided to two group. Thirty-one patients were treated with oral fluconazole (100 mg twice a day) for 6 weeks and 29 patients were treated with intra-muscular glucantime (20 mgSb/kg) for 21 days. Both groups were evaluated 3 and 6 weeks after onset of treatment. T-test and Chi-square test were used for statistical analyses and (P0.05). Conclusion: It seems that efficacy of fluconazole in acute cutaneous leishmaniasis is lower than glucantime. A larger clinical trial is recommended.