Abstract: Objective: To explore the mechanism of Xiaoqinglong Decoction on improving mucociliary clearance function of CFTR ion channel based on cAMP pathway by observing the dynamic changes of cAMP,cystic fibrosis transmembrane conductance regulator (CFTR),and MUC5AC expression in asthma mice with syndrome of cold-rheum accumulation in the lung. Methods: Model mice with asthma with syndrome of cold-rheum accumulation in the lung were established by ovalbumin (OVA) plus cold stimulation. After the last stimulation, lung tissues were stained with hematoxylin-eosin (HE) and Alcian blue-periodic acid Schiff (AB-PAS). Bronchoalveolar lavage fluid and lung tissue supernatants were collected, and the levels of MUC5AC in bronchoalveolar lavage fluid and the levels of cAMP and CFTR in lung tissue supernatants were detected. Results:Model mice with asthma with syndrome of cold-rheum accumulation in the lung were successfully established. The expression of MUC5AC in bronchoalveolar lavage fluid was increased, and the expression of cAMP and CFTR in lung tissue supernatants was decreased. Histological sections showed inflammatory cells infiltration around the airways, mucus secretion and hyperplasia of goblet cells. Compared with that in the model group, the expression of MUC5AC in bronchoalveolar lavage fluid was decreased in the Dexamethasone group and the Xiaoqinglong Decoction group, and the decrease of expression of MUC5AC in bronchoalveolar lavage fluid in the Xiaoqinglong Decoction group was smaller than that in the Dexamethasone group, differences being significant (P<0.05). Compared with that in the model group,the expression of cAMP and CFTR in the lung tissue supernatants was increased in the cAMP group and the Xiaoqinglong Decoction group respectively, and the increase of expression of cAMP and CFTR in the lung tissue in the Xiaoqinglong Decoction group was smaller than that in the cAMP group,differences being significant (P<0.05). According to histological sections, there was almost no inflammatory cell infiltration around the bronchi in the Xiaoqinglong Decoction group; the bronchial wall and alveoli were relatively intact; the smooth muscle hyperplasia and bronchial thickening were less severe than those in the cAMP group and Dexamethasone group, and no mucus plugs or exfoliated alveolar epithelium were seen in the lumen. The bronchial wall was clear in the Xiaoqinglong Decoction group; the hyperplasia of goblet cells was less,and less mucus was secreted in the airways than that in the cAMP group and Dexamethasone group. Conclusion:Xiaoqinglong Decoction can alleviate airway mucus hypersecretion in asthma mice with syndrome of cold-rheum accumulation in the lung and guarantee mucociliary clearance function, and its mechanism is to enhance CFTR ion channel through cAMP pathway.