Abstract: OBJECTIVE To investigate the clinical effect of Guben Peiyuan Decoction on treatment of chronic obstructive pulmonary disease（COPD） patients complicated with frailty. METHODS A total of 102 patients with COPD complicated with weakness who were treated in the hospital from Jun 2019 to Feb 2021 were randomly divided into control group and study group by using random number table method, with 51 patients in each group. Both groups received routine treatment, the study group was treated with Guben Peiyuan Decoction on the basis of the control group. The therapeutic effects of the two groups were analyzed, the pulmonary function indexes forced expiratory volume in the first second（FEV₁）, forced vital capacity（FVC） and FEV₁/FVC, the expression of mitogen-activated protein kinases（MAPK） signaling pathway related proteins extracellular regulated protein kinase（ERK）, p38 and c-Jun, and the levels of airway remodeling related factors serum connective tissue growth factor（GTGF）, basic fibroblast growth factor（b-FGF）, transforming growth factor β1（TGF-β1）, Smad3, cartilage glycoprotein 39（YKL-39） and activin A were compared between the two groups. RESULTS The effective rates of the two groups was 94.12% and 80.39%, respectively, which were different（P＜0.05）. After treatment, the symptom scores of the two groups were significantly reduced（P＜0.05）, and the study group was significantly lower than the control group（P＜0.05）. After treatment, the FEV₁, FVC and FEV₁/FVC in the two groups were significantly increased（P＜0.05）, and the study group was significantly higher than the control group（P＜0.05）. After treatment, the incidence of pulmonary infection in the study group was 5.88%, significantly lower than that in the control group（19.61%）（χ~2=4.320,P=0.038）. After treatment, the relative expression levels of ERK, p38 and c-Jun mRNAs in serum and induced sputum of the study group were significantly lower than those in the control group（P＜0.05）, the levels of airway remodeling related factors in the study group were significantly lower than those in the control group（P＜0.05）. CONCLUSION Guben Peiyuan Decoction can reduce the incidence of pulmonary infection, improve lung function and clinical symptoms, inhibit airway remodeling, and hinder the MAPK signaling pathway in patients with COPD complicated with weakness.