Abstract: Objective: To study the regulation effect of Zeqi Decoction on the lung function and neutrop extracellular traps (NETs) in mice with chronic obstructive pulmonary disease (COPD) through phosphatidylinositol 3-kinase (PI3K)/serine threonine kinase (AKT) signaling pathway. Methods:A total of 32 BALB/c male mice were randomly divided into the control group,the model group,Zeqi Decoction group and Dexamethasone group,with eight mice in each group. Except for the control group, the COPD model was established by cigarette smoke inhalation for 12 weeks in the other three groups;from the 9th to 12th week,the control group and the model group were given 0.9% sodium chloride solution at a dosage of 0.2 mL(/ kg·d) by gastric gavage,Zeqi decoction group was given 0.171 g/mL Zeqi Decoction at a dosage of 0.2 mL(/ kg·d) by gastric gavage,and Dexamethasone group was given Dexamethasone at a dosage of 2 mg(/ kg·d) by gastric gavage. The forced expiratory volume in 0.3 s( FEV0.3)/forced vital capacity( FVC), minute ventilation volume (MV),enhanced pause (Penh),mean linear intercept (MLI) in lung tissue, bronchial wall thickness (BWT), the levels of interleukin (IL)-2, IL-6, IL-17 A and IL-18 in serum and lung tissue, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), the expression levels of neutrophil elastase (NE), citrullinated histone H3 (Cit H3), phosphorylated PI3K (p-PI3K), phosphorylated AKT (p-AKT) and the content of myeloperoxidase (MPO)-DNA complex in lung tissue were detected. Results:After four weeks of intervention,the FEV0.3/FVC,MV,SOD and GSH-PX of the mice in the model group were lower than those of the mice in the control group (P<0.05),and the Penh,MLI,BWT,IL-2,IL-6,IL-17 A,IL-18,MDA,NE,Cit H3,MPO-DNA,p-PI3K and p-AKT were higher than those of the mice in the control group( P<0.05);the FEV0.3/FVC,MV,SOD and GSH-PX of the mice in Zeqi Decoction group and Dexamethasone group were higher than those of the mice in the model group (P<0.05),and the Penh,MLI,BWT,IL-2,IL-6, IL-17 A,IL-18,MDA,NE,Cit H3,MPO-DNA,p-PI3K and p-AKT were lower than those of the mice in the model group (P<0.05);the levels of NE,Cit H3,MPO-DNA,p-PI3K and p-AKT in Zeqi Decoction group were lower than those of the mice in Dexamethasone group (P<0.05),and there was no statistically significant difference being found in the comparisons of remaining indexes between Zeqi Decoction group and Dexamethasone group (P> 0.05). Conclusion: Zeqi Decoction can improve the lung function and pathological changes of lung tissue in COPD mice, and reduce the inflammatory responses and oxidative stress. Its inhibition of the NETs formation mediated by PI3K/AKT signaling pathway may be the related molecular mechanism.