Background: The presence of pharmaceutical substances and their residual in water resources is an important environmental concern. Azithromycin, an antibiotic that is used for the treatment of infectious diseases, is a pollutant agent in the wastewater. The aim of this study was to investigate azithromycin degradation in aqueous solution through ultrasonic process in the presence of zinc oxide nanoparticles as catalysts. Methods: Sonocatalytic experiments were performed at variable conditions including pH (3-8), temperature (20-60°C), time (3-21 minutes), catalyst dosage (0.25-2 g/L), hydrogen peroxide concentration (15-100 mg/L) and initial azithromycin concentration (10-100 mg/L). Results: The optimum values for pH (3), temperature (40°C), time (15 minutes), catalyst dosage (1 g/L), H 2 O 2 concentration (50 mg/L) and initial azithromycin concentration (20 mg/L) were determined. The highest degradation efficiency of 98.4% was achieved after 15 minutes of ultrasonic irradiation under optimum condition. Conclusion: According to the results, ultrasonic irradiation is able to degrade azithromycin. In addition, ZnO and hydroxyl radical can successfully accelerate the reaction process in the shortest possible time.