Abstract： Objective： To observe the clinical effect of modified Sangju Zhisou Powder combined with Azithromycin sequential therapy on mycoplasma pneumonia (MP) infection in children with wind-heat syndrome. Methods：A total of 102 children with MP infection with wind-heat syndrome were divided into the treatment group and the control group according to the radom rumber table method，with 51 cases in each group. The treatment group was treated with modified Sangju Zhisou Powder combined with Azithromycin sequential therapy， and the control group was only treated with Azithromycin sequential therapy. After two weeks of treatment，the clinical effects，traditional Chinese medicine (TCM) syndrome scores， remission time of symptoms and levels of serum inflammatory factors [interferon- γ (IFN- γ)， C-reactive protein (CRP) and tumor necrosis factor- α (TNF- α)] were compared between the two groups. Results：After treatment，the total effective rate was 98.04% in the treatment group，higher than that of 86.27% in the control group， the difference being significant (P＜0.05). The disappearance time of fever， cough， expectoration and rales in the treatment group was respectively shorter than that in the control group， the difference being significant (P＜0.05). After treatment， the TCM syndrome scores in the two groups were reduced when compared with those before treatment (P＜0.05)， and the TCM syndrome score in the treatment group was lower than that in the control group (P＜0.05). After treatment，the levels of serum IFN- γ， CRP and TNF- α in the two groups were declined when compared with those before treatment (P＜0.05)，and the above three levels in the treatment group were lower than those in the control group (P＜0.05). Conclusion： The therapy of modified Sangju Zhisou Powder combined with Azithromycin sequential therapy has a significant curative effect on MP infection with wind-heat syndrome， which can effectively reduce the inflammatory responses of the body，improve the TCM syndrome and accelerate the recovery.