Background: Pityriasis rosea is an acute, inflammatory and self-limited disease, which is characterized by a primary scaly plaque (Herald patch) followed by a generalized, symmetrical papulosqumous eruption (Mostly on trunk and proximal extremities). Objective: To determine the efficacy of erythromycin in the treatment of patients with pityriasis rosea. Patients and Methods: In this double-blind randomized clinical trial, 46 patients with pityriasis rosea in two equal groups were treated with oral erythromycin 1gr per day or placebo for seven days and were followed 1, 2 and 6 weeks after treatment. The response to the treatment was evaluated as complete, partial and no response. Results: In 48% of the case group and 13% of the control group complete response was seen at the end of first week of treatment. Moreover, these rates reached 91% and 57% at the end of second week, 100% and 87% at the end of sixth week, respectively. The differences between two groups were statistically significant after first and second weeks. Conclusion: Oral erythromycin was effective in the treatment of patients with pityriasis rosea. Also, it reduces the duration of disease.