Objective To investigate the three Tiao-Bu Fei-Shen therapies in improving airway mucus hypersecretion in stable chronic obstructive pulmonary disease (COPD) rats. Methods 90 rats were randomly divided into nine groups: control group, COPD group, Bu-Fei Jian-Pi (BJF) group, Bu-Fei Yi-Shen (BYF) group, Yi-Qi Zi-Shen (YZF) group, ERK1/2 inhibitor (PD98059) group, BJF + PD98059 group, BYF + PD98059 group and YZF + PD98059 group. The rat model of COPD was established by exposing them to cigarette smoke and repeated bacterial infection from the first to the eighth week. From the ninth to the sixteenth week, the Control group and the COPD group were given normal saline 2 ml, the TCM treatment group was given three Tiao-Bu Fei-Shen formulas by gavage, and the inhibitor group and the combination group were given PD98059 by intraperitoneal injection for 7 days. Lung function tests were conducted at the end of 16 weeks along with assessments on lung tissue morphology, lung water content,inflammatory cell count in bronchoalveolar lavage fluid (BALF), and level of inflammatory factors in serum. AB-PAS staining was used to determine goblet cell proportion while immunohistochemistry was employed to measure Muc5AC and Muc5B expression levels. PCR analysis was performed to detect ERK1/2 mRNA expression as well as ENaC, CFTR, AQP5 mRNA expressions. Western Blot analysis measured protein expression levels of ERK1/2and P-ERK1/2 in lung tissue. Results Compared with the Control Group, TV, MV, FVC, FEV0.1, FEV0.1/FVC significantly decreased (P<0.01) in COPD Group.Lung pathology revealed alveolar disorder, massive fracture of alveolar wall, and severe shrinkage/thickening of airway wall accompanied by extensive infiltration of inflammatory cells. Water content in lung tissue increased significantly (P<0.01). The proportion of macrophages in BALF was significantly reduced (P<0.01), whereas the proportions of neutrophils and lymphocytes were significantly increased (P<0.01). The level of TNF-α and IL-1β in serum were significantly increased (P<0.01). The percentage of goblet cells and expression levels of Muc5AC and Muc5B in airway epithelial cells exhibited a significant increase (P<0.01). Expression levels of ERK1, ERK2, and ENaC mRNA in lung tissue were significantly elevated (P<0.01), while expression levels of CFTR and AQP5 mRNA were significantly decreased (P<0.01). Compared to the COPD group, the treatment groups demonstrated improvements in the aforementioned indicators (P<0.05), with the three Tiao-Bu Fei-Shen formulas combined PD98059 group showing superior efficacy compared to single treatment groups (P<0.05). Conclusions Three Tiao-Bu Fei-Shen therapies can ameliorate airway mucus hypersecretion in COPD rats by inhibiting the ERK1/2 signaling pathway.