Objective To investigate the effects and mechanisms of peimine (PME) on chronic obstructive pulmonary disease (COPD) in mice.   Methods The mice were randomly divided into 4 groups (20 mice in each group), control group, PME group, chronic obstructive pulmonary disease group and treatment group. Animal models of COPD were induced in mice by lipopolysaccharide combined with smoke. The effects of PME on COPD model mice was analyzed by HE staining, transmission electron microscopy and the ratio of wet/dry weight of mouse lung tissue. The effects of PME on COPD model mice were analyzed by HE staining, transmission electron microscopy and the ratio of wet/dry weight of mouse lung tissue. The effects of PME on inflammatory factor tumor necrosis factor (TNF)-α, interleukin(IL)-6 and IL-1β in lung tissue were analyzed by ELISA and Western blotting. The effects of PME on oxidative stress in lung tissue were analyzed by dihydroethidium (DHE) staining and Western blotting. The effects of PME on nuclear factor kappa-B (NF-κB) pathway and nuclear factor erythroid 2-related factor 2(Nrf2) pathway were analyzed by protein immunoblotting.      Results Compared with the COPD group, PME treatment could significantly improve the lung tissue injury and the number of inflammatory cells in mice, and the wet/dry weight ratio of lung tissue was significantly reduced. Compared with the control group, the levels of TNF-α, IL-6 and IL-1β in the alveolar lavage fluid of COPD mice significantly increased, and the level of TNF-α, IL-6 and IL-1β in the alveolar lavage fluid of mice after PME treatment was significantly reduced. In addition, compared with the control group, the protein expression of TNF-α, IL-6 and IL-1β in the lung tissue of COPD mice significantly increased, and the level of TNF-α, IL-6 and IL-1β in the lung tissue of COPD mice after PME treatment were significantly reduced. Immunohistochemistry and Western blotting showed that the level of superoxide dismutase 2(SOD2) protein in COPD group was significantly lower than that in control group, while PME treatment could improve the level of superoxide dismutase protein. The analysis of MDA content in lung tissue showed that compared with the COPD group, the production of MDA in lung tissue of COPD mice was significantly inhibited after PME treatment. Protein Western blotting showed that PME treatment could prevent the phosphorylation of inhibitor of NF-κB(IκBα) and the transfer of NF-κB p65 to the cell nucleus, and the expression of Nrf2 and its main downstream target heme oxygenase-1(HO-1) in the lung tissue of mice treated with PME significantly increased.  Conclusion PME is able to inhibit inflammation and oxidative stress and improve lung tissues damage in the COPD model in vivo and this protection effect might be both the Nrf2 pathway activation and NF-κB pathway inhibition.