Abstract: Objective To study the effects of budesonide combined with azithromycin sequential therapy on mycoplasma pneumoniae pneumonia (MMP) in children. Methods A total of 120 patients were randomly divided into four groups according to random number table method: group A, group B, group C and group D, with 30 cases in each group. Group A received azithromycin, 10 mg/kg, intravenous instillation, 1 time/day for 3 days; after withdrawal for 4 days, azithromycin dry suspension was given to patients, 10 mg/kg, oral, 1 time/day, for 7 days. Group B received azithromycin for 5 days and after withdrawal for 4 days, azithromycin dry suspension was given to patients for 5 days. On the basis of group A, Group C received additional budesonide, 1 mg, aerosol inhalation, 1 time/ day, for 14 days. On the basis of group B, Group D received additional budesonide for 14 days. After the treatment of 14 days, the total effective rates, disappearance times of symptoms and signs, pulmonary function, levels of C-reactive protein (CRP), IL-6 and TNF-α, and the incidences of adverse reactions in the four groups were observed and compared. Results After the treatment, the total effective rates of group C (93.3%) and group D (96.6%) were much higher than group A (73.3%) and group B (73.3%). The disappearance times of symptoms and signs of group C and group D were much shorter than that in group A and group B, which were significantly different (all P<0.05). After the treatment, FEV1, FVC, PEF, CRP, IL-6 and TNF-α were much better than before the treatment in all the four groups (all P<0.05), and these in group C and group D were better than group A and group B (all P<0.05). The total incidences of adverse reactions of group A (10.0%) and group C (6.7%) were much lower than group B (36.7%) and group D (30.0%), which were significantly different (all P<0.05). Conclusion Budesonide combined with azithromycin sequential therapy in children with MPP is more effective, which can shorten the courses of disease and ameliorate pulmonary functions and the levels of inflammatory factors; furthermore, it is more safety for using intravenous injection of azithromycin for 3 days.