This research aimed to describe the effect of azithromycin combined with fluticasone propionate aerosol inhalation on immune function in children with chronic cough caused by Mycoplasma pneumoniae (MP) infection. This study was a retrospective analysis in which 110 children with chronic cough caused by MP infection were divided into two groups based on different treatment methods: 58 cases in the control group treated with azithromycin dry suspension and 52 cases in the intervention group treated with azithromycin dry suspension and fluticasone propionate inhalation aerosol. Lung function, inflammatory factors, immune indicators, laboratory-related indicators, adverse reactions, and therapeutic effects were compared between the two groups. Compared with the pre-treatment period, levels of FEV1, FVC, and PEF increased post-treatment in both groups, with higher levels observed in the intervention group (all P < 0.05). IL-17, IL-6, and IL-10 levels decreased post-treatment in both groups, with the intervention group showing lower levels (all P < 0.05). The levels of IgG, IgA, IgM, CRP, ESR, and PCT decreased in both groups, with the intervention group showing lower levels (all P < 0.05). Higher treatment effectiveness rates were observed in the intervention group compared to the control group (P < 0.05). The incidence of adverse reactions did not differ significantly between the two groups (P > 0.05). Conclusion: Azithromycin dry suspension combined with fluticasone propionate aerosol inhalation in children with chronic cough due to MP infection reduces inflammatory factors, improves immune function, and enhances treatment efficacy.