Objective To explore the effect of Zeqi Huatan Formula（ZHF

泽漆化痰方） on chronic obstructive pulmonary disease（COPD） model rats with airway mucus hypersecretion as well as the underlying mechanism. Methods Twenty-eight Wistar rats were randomly divided into blank group

model group

ZHF group and AG1478 group

with seven rats in each group. Except for the blank group

smoking combined with airway instillation of lipopolysaccharide（LPS） were used to establish COPD airway mucus hypersecretion rat model. Two weeks after the modelling

ZHF group was given ZHF extract powder by gavage daily at a dose of 1 g/100 g body weight

while AG1478 group was administered with AG1478 by gavage at a dose of 0-8 mg/100 g body weight

both for two consecutive weeks; the rats in the blank group and the model group were not gavaged. At the end of the fourth week

blood was collected from the abdominal aorta

and the bronchoalveolar lavage fluid（BALF） and lung tissue samples were obtained. HE and PAS staining were used to explore the airway histopathological changes. ELISA method was used to detect the content of tumor necrosis factor-α（TNF-α） and interleukin 8（IL-8） in BALF

and RT-PCR method was used to detect the gene expression of mucin 5 AC（MUC5 AC） in the lung tissues of rats. Western blotting was used to detect the expression of specific protein 1（SP1）

phosphorylated specific protein 1（p-SP1）

epidermal growth factor receptor（EGFR）

phosphorylated epidermal growth factor receptor（p-EGFR）

and MUC5 AC protein in the lung tissues. Results Compared to the blank group

in the model group there were airway epithelial goblet cells hyperplasia

submucosal gland hypertrophy

and local inflammatory cell infiltration; the contents of TNF-α and IL-8 in BALF increased; the gene expression of MUC5 AC in the lung tissues increased; the expression of p-EGFR/EGFR

p-SP1/SP1

MUC5 AC protein increased（P<0.05）. Compared to those in the model group

the degree of airway epithelial goblet cell proliferation was reduced in AG1478 group and ZHF group; the TNF-α and IL-8 levels in BALF decreased; the MUC5 AC gene expression in the lung tissue decreased; the expression of p-SP1/SP1 and MUC5 AC protein decreased（P<0.05）. ZHF group was better than AG1478 group in reducing the TNF-α and IL-8 levels in BALF（P<0.05）. Conclusion ZHF may inhibit the hypersecretion of airway mucus in COPD rats possibly by reducing inflammation

decreasing the MUC5 AC gene expression in lung tissue

and down-regulating the expression of EGFR signaling pathway-related proteins.