Objective To investigate the effect of fludostane combined with budesonide on the levels of serum soluble myeloid cell trigger receptor-1 (strom-1), pulmonary surfactant protein D (SP-D), interferon-γ (IFN-γ) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods 80 patients with AECOPD admitted to our hospital from June 2016 to December 2019 were selected as the study objects. According to the random number table method, patients were divided into observation group and control group, 40 cases in each group. The patients in the two groups received routine treatment, the control group was treated with fludostame, and the observation group was treated with budesonide on the basis of the control group. The pulmonary function (FEV1, PEF, FEV1/FVC) and inflammatory indexes of the two groups before and after treatment were compared, and the adverse reactions of the two groups were compared. Results After treatment, FEV1, PEF and FEV1 / FVC in the observation group were higher than those in the control group, with a statistically significant difference (P< 0.05); SP-D and strom-1 levels in the observation group were lower than those in the control group, and IFN-γ levels were higher than those in the control group, with a statistically significant difference (P < 0.05); there was no statistically significant difference in the incidence of adverse reactions between the two groups (P > 0.05). Conclusion The combination of fludostane and budesonide in the treatment of AECOPD patients has a significant clinical effect,which can effectively reduce the inflammatory response, improve the pulmonary function of patients, and has a certain degree of safety.