Abstract: Objective To investigate the efficacy of different treatment courses of nebulized budesonide in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) and its mechanism on airway inflammation. Methods A total of 120 patients with acute exacerbation of COPD admitted to Huai'an Huai'an Hospital from January 2022 to December 2024. The patients were randomly divided into an intervention group and a control group, with 60 cases in each. The control group received nebulization inhalation of budesonide suspension at 2 mg per dose, twice daily for two treatment courses, with each course lasting 5 days. The intervention group also received the same regimen for four 5-day treatment courses. The clinical efficacy, inflammatory factors, airway remodeling, pulmonary function, and incidence of adverse reactions were compared between the two groups. Results After treatment, the total effective rate in the intervention group was higher than that in the control group. The levels of tissue inhibitor of metalloproteinase-1 (TIMP-1), leukotriene B4 (LT-B4), and transforming growth factor-β1 (TGF-β1) in the intervention group were lower than those in the control group. The wall area and lumen area in the intervention group were larger than those in the control group, while the tracheal wall thickness was smaller. Forced expiratory volume in one second (FEV₁) and FEV₁/FVC ratio were higher in the observation group compared to the control group (P ＜ 0.05). In both groups, TIMP-1, LT-B4, and TGF-β1 levels decreased compared to before treatment; wall area and lumen area increased compared to before treatment; tracheal wall thickness decreased compared to before treatment; and FEV₁ and FEV₁/FVC increased compared to before treatment (P ＜ 0.05). At 3 months and 1 year after treatment, the COPD assessment test scores decreased in both groups, and were lower in the intervention group than in the control group (P ＜ 0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups during treatment (P ＞ 0.05). Conclusion A longer treatment course of nebulized budesonide for acute exacerbation of COPD can improve therapeutic efficacy, reduce the levels of inflammatory factors, and enhance lung function.