Background and aim: Pentavalent antimony compounds are the first line treatment for cutaneous leishmaniasis. Clinical resistance to pentavalent antimony in the form of meglumine antimoniate (Glucantime) has been recognized as a problem in leishmaniasis. Herein, clinical response to Glucantime were studied in patients suffered from cutaneous leishmaniasis.Materials and Methods: In a cross-sectional study 370 patients with cutaneous leishmaniasis were treated with systemic Glucantime, 50 mg/kg/day, for 2 to 3 weeks. They were visited weekly for 3 weeks and also followed up for 3 months after treatment was completed. The clinical and parasitological response to this treatment was evaluated, and classified into partial and complete response and failure to treatment. Results: Two hundred forty-seven men and 123 women were followed up. The mean age was 36.7±16 years. There were 64.1% partial response after 2 weeks and 73% partial response at the third week of treatment. 11.6% of lesions were not cured after 3 weeks of treatment and 8.1% were not still cured 12 weeks thereafter.Conclusion: Clinical resistance to Glucantime is an important problem. The mechanisms of resistance and using drug combinations are needed to be considered.