Objective: To explore the effects of oscillatory positive expiratory pressure device (OPEPD) combined with aerosol inhalation of salbutamol in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: A total of 120 patients with AECOPD admitted to Ganzhou Fifth People"s Hospital were enrolled as the research objects. According to random number table method, they were divided into control group (60 cases, aerosol inhalation of salbutamol) and treatment group (60 cases, OPEPD on basis of control group). The sputum changes after 1d and 14d of treatment, lung function, disease severity and inflammatory factors in the two groups were compared. Results: Compared with control group at 14d after treatment, sputum volume was increased, and score of sputum color was decreased in treatment group (P<0.05). FVC, FEV1 and FEV1/FVC in treatment group were higher than those in control group, while scores of Borg and CAT, levels of CRP and IL-6 were lower than those in control group (P<0.05). Conclusion: OPEPD combined with aerosol inhalation of salbutamol can promote expectoration, reduce levels of inflammatory factors, improve lung function and dyspnea symptoms in AECOPD patients.