〔Abstract〕 Objective To explore the therapeutic effect of Xuanfei Zhisou mixture combined with azithromycin on children with mycoplasma pneumonia. Methods A total of 200 children with mycoplasma pneumonia admitted to Gaoxin Hospital of the First Affiliated Hospital of Nanchang University from October 2022 to October 2023 were selected and randomly divided into two groups, 100 cases in each group. The control group was treated with azithromycin alone, and the observation group was treated with Xuanfei Zhisou mixture on the basis of the control group. The rate of bronchial mucosal injury, pulmonary function indicators, clinical symptom scores, levels of inflammatory factors, and adverse effects were compared between the two groups. Results The rates of mucosal congestion, edema, mucosal follicle-like hyperplasia, bronchial opening redness and mucosal erosion in the observation group were significantly lower than those of the control group, and the differences were statistically significant (P < 0.05). After treatment, the lung function related indexes [forced expiratory volume in first second / forced vital capacity (FEV1/FVC), maximum mid expiratory flow rate (MMF), maximum vital capacity (VCmax), peak expiratory flow (PEF), maximum voluntary ventilation (MVV) and FEV1% predictive value] in the two groups increased, and those in the observation group were higher than the control group, the differences were statistically significant ( P < 0.05 ). After treatment, the scores of cough, loss of appetite, wheezing, and fever were decreased in the two groups, and those in the observation group were lower than the control group, the differences were statistically significant (P < 0.05 ). After treatment, the serum levels of inflammatory factors decreased in both groups, and the serum levels of procalcitonin (PCT), matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-α (TNF-α), and interleukin-8 (IL-8) were significantly lower than those of the control group, with statistically significant differences (P < 0.05). There is no statistically significant difference in the incidence of diarrhea, rash, abdominal pain, and nausea and vomiting between the two groups of children (P > 0.05). Conclusion Xuanfei Zhisou mixture combined with azithromycin has a significant effect in the treatment of children with mycoplasma pneumonia, which can effectively improve lung function and repair bronchial mucosal injury.