〔Abstract〕 Objective To study the clinical effect of low dose erythromycin combined with Montelukast sodium on children with asthma. Methods A total of 90 children with asthma diagnosed and treated in the First Affiliated Hospital of Henan University of Science and Technology from January 2020 to June 2022 were selected and divided into an observation group and a control group by randomized control method, with 45 cases in each group.The control group was treated with Montelukast sodium, and the observation group was treated with low-dose erythromycin combined with Montelukast sodium. The differences of efficacy, complications, lung function, childhood asthma control test (C–ACT) score, inflammatory factors and T lymphocytes were compared between the two groups. Results The total effective rate of the observation group was higher than that of the control group, and the difference was statistically significant (P < 0.05). The incidence of gastrointestinal symptoms, liver and kidney function injury, lethargy and arrhythmia in the observation group were higher than those in the control group, but the differences were not statistically significant (P > 0.05). After treatment, forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), peak expiratory flow (PEF) and C-ACT score in the observation group were higher than those in the control group, and the differences were statistically significant (P < 0.05). Leukotriene D4 (LTD4), tumor necrosis fact-α (TNF-α), CD3+ , CD4+ and CD8+ in the observation group were lower than those in the control group after treatment, and the differences were statistically significant (P < 0.05). Conclusion Low dose erythromycin combined with Montelukast sodium can improve lung function and inflammatory response in children with asthma, and has the advantages of high efficiency and safety.