Objective: To investigate the effect of Zhenqi Fuzheng granules combined with salbutamol in the treatment of acute exacerbation of chronic obstructive pulmonary disease. Methods: 92 patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) in our hospital from October 2022 to November 2024 were randomly divided into two groups (n=46) using a lottery method. The control group received salbutamol, while the observation group received Zhenqi Fuzheng granules combined with salbutamol. Compare the differences in effective rate, lung function, and immune function indicators between two groups. Results: The effective rate of the observation group was significantly higher than control group (P<0.05). Before treatment, there was no significant difference in the maximum ventilation volume (MVV), maximum inspiratory pressure (MIP), peak expiratory flow rate (PEF), maximum expiratory pressure (MEP), and forced vital capacity (FVC) between the two groups (P>0.05). After treatment, the MVV, MIP, PEF, MEP, and FVC in the observation group were higher than those in the control group (P<0.05). Before treatment, there was no significant difference in CD3+, CD4+/CD8+, and CD4+values between the two groups (P>0.05). After treatment, the observation group had higher CD3+, CD4+/CD8+, and CD4+values (P<0.05). There was no significant difference in the incidence of headache, pharyngeal discomfort, gastrointestinal reactions, hand tremors, and palpitations between the two groups (P>0.05). Conclusion: Zhenqi Fuzheng granules combined with salbutamol can improve the immune function and lung function of patients with acute exacerbation of chronic obstructive pulmonary disease, which is safe and effective.