Objective To study the effect and mechanism of atorvastatin on improving airway function of mice with chronic obstructive pulmonary disease (COPD) by inhibiting the expression of inducible nitric oxide synthase (iNOS). Methods Wild type (WT) mice were randomly divided into WT control group, WT+COPD group, WT+COPD+atorvastatin group, NC lentivirus group, NC lentivirus+COPD group, NC lentivirus+COPD+atorvastatin group, and iNOS lentivirus+COPD+atorvastatin group. Lung specific iNOS knockout (KO) mice were randomly divided into KO control group and KO+COPD group. The COPD model was established by passive inhalation of cigarette smoke. Atorvastatin (10 mg·kg–1·d–1) was given by gavage, and the negative control (NC) lentivirus or iNOS lentivirus was given by tail vein injection. The lung function indexes including peak inspiratory flow (PIF) and peak expiratory flow (PEF), the number of neutrophils (N), eosinophils (E), lymphocytes (L) and Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF), the expression levels of iNOS, endothelium nitric oxide synthase (eNOS) and neural nitric oxide synthase (nNOS) in lung tissue were measured. Results Compared with WT control group, the levels of PIF and PEF decreased, typical pathological changes of COPD appeared in lung tissue, the numbers of N, E, L and the contents of TNF-α, IL-1β in BALF, the expression of iNOS, eNOS and nNOS in lung tissue increased in WT+COPD group (all P<0.05). After atorvastatin intervention, the levels of PIF and PEF increased, the pathological changes of COPD in lung tissue ameliorated, the numbers of N, E, L and the contents of TNF-α, IL-1β in BALF, the expression of iNOS in lung tissue decreased in WT+COPD+atorvastatin group (all P<0.05). After specific knockout of iNOS in lung tissue, the levels of PIF and PEF increased, the pathological changes of COPD in lung tissue ameliorated, the numbers of N, E, L and the contents of TNF-α, IL-1β in BALF decreased in KO+COPD group (all P<0.05). After overexpression of iNOS by tail vein injection of lentiviral, the levels of PIF and PEF decreased, the pathological changes of COPD in lung tissue aggravated, the numbers of N, E, L and the contents of TNF-α, IL-1β in BALF increased in iNOS lentiviral+COPD+atorvastatin group (all P<0.05). Conclusion The effect of atorvastatin on improving airway function and inflammatory response of COPD mice is related to the inhibition of iNOS expression.