OBJECTIVE: To explore the clinical effect of Traditional Chinese Medicine (TCM) plus azithromycin in the treatment of Mycoplasma pneumonia (MP). METHODS: This was a retrospective study including the clinical data of 119 patients with MP treated at Taihe County Hospital of Traditional Chinese Medicine from April 2021 to November 2023. According to treatment records, 58 cases were treated with conventional therapy and azithromycin (azithromycin group), and 61 cases were treated with conventional therapy, azithromycin, and Xiaoxianxiong decoction and Weijing decoction and acupoint application (TCM + azithromycin group). The treatment outcomes, levels of inflammatory status indicators before and after treatment, respiratory function status, and incidence of adverse reactions were analyzed between the two groups. RESULTS: The overall effective rate of TCM + azithromycin group was significantly higher than that of azithromycin group ( CONCLUSION: Compared with treatment with azithromycin alone, intervention with TCM + azithromycin can significantly improve the respiratory function of patients with MP, reduce the degree of inflammatory response, and enhance the overall treatment effect without increasing the incidence of adverse reactions. CORE TIP: This study indicates that intervention with traditional Chinese medicine and azithromycin can significantly improve the respiratory function of MP patients, reduce the degree of inflammatory response, improve overall treatment efficacy, and is safe.