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Background and Objective: Treatment of Cutaneous leishmaniasis (CL) with oral therapeutic drugs, ideally cheap, with good tolerance and safe are highly desirable.The aim of this study was to assess the efficacy of azithromycin (AZ) for treatment of patients with CL in Ahvaz – Iran. Materials and Methods: In a randomized controlled clinical trial study, 28 patients with CL as cases (AZ group) and 26 patients as control (C group) were studied. Cases were treated orally 500 mg/day of azithromycin in single dose for 28 days. Patients in control group did not receive any treatment. Both groups were followed up in days 14, 28 and month 2 and 5. Data were analyzed in SPSS-11.5 by using chi square and exact Fisher's tests. Results: Means±SD age of subjects was 20.26±8.45 years. Male to female ratio was 1.5:1. The half of the patients resided in rural area. At the end of study treatment. 46.4% of patients in AZ group and 15.4% of patients in control group were cured (P<0.02). One relapse of CL was observed in AZ group, no serious drug side effects was observed. Conclusion: This study showed that azithromycin has an acceptable effect on the treatment of cutaneous leishmaniasis in Iranian patients and can be used alternatively in treatment of cutaneous leishmaniasis.