Background: Mastitis is an inflammatory disorder in breast tissues due to bacterial factors, mycobacterial infections or autoimmune diseases. Idiopathic granulomatous mastitis (IGM) is a form of mastitis which may be affected by systematic diseases such as sarcoidosis, and infectious causes such as mycobacterium and fungus. This study evaluates the efficacy of medical therapy with a combination of corticosteroid and Azithromycin in patients with IGM. Materials and Methods: This study is a clinical trial research carried out in Alzahra Hospital (Isfahan, Iran) in 2013 on granulomatous mastitis patients. It was administered 250 mg of Azithromycin per 12 hour and 60 mg of Prednisolone per day within 2 weeks. Next, they took 40 mg/day within 8 weeks, and this dosage was tapered during 6 months and the patients clinically and radiologically followed up. The studied patients were examined within 1 week, 2 weeks, 1 month, 3 months, and 6 months, from the beginning of treatment. Results: This study investigated granulomatous mastitis patients in Alzahra hospital in 2013. The mean age of these patients was 33.6 ± 8.9, and their age range was 18–56 years old. Among 26 studied patients, 24 persons (92.3%) according to follow-up the patients by physical examination and sonography responded to treatment of corticosteroid and Azithromycin. The remaining (7.7%) underwent surgery. Treatment periods in case of drug use were respectively, 8.5 ± 0.71 months. Conclusion: Treatment with corticosteroid and Azithromycin is an effective and appropriate treatment for IGM.