Objective To explore whether depression can occur in COPD mouse model induced by chronic exposure to tobacco smoke alone. Methods SPF grade mice were divided into control group（CLT group） and smoke exposure group（CS group）. Mice in CS group were exposed to tobacco smoke for 24 weeks. Open field test and tail suspension test were performed 24 hours after the last smoking，and lung function test was performed after the test. The levels of IL­6 and KC in BALF supernatant were detected by ELISA， as well as the serum levels of 5­HT. H&E staining and Nissl staining were used to observe the pathological changes of lung and brain tissues of mice. Results Compared with CTL group，the body weight of mice in CS group grew slowly （P < 0.001）， FRC and FVC were significantly increased （P < 0.001），and FEV20/FVC and FEV50/FVC were significantly decreased （P < 0.05）. The expression levels of proinflammatory cytokines IL­6 and KC in BALF were increased （P < 0.01），and the content level of 5­HT in serum was significantly decreased （P < 0.001）. The total movement distance， the number of times into the central area and the retention time in the central area of the CS group were significantly decreased in the open field test （P < 0.05）， and the immobility time of the CS group was increased in the tail suspension test （P < 0.05）. H&E staining showed that the mean alveolar intercept of lung tissue in the CS group was significantly increased （P < 0.001）， and Nissl staining showed that the number of damaged neurons in the cortex （P < 0.001） and hippocampus （P < 0.01） in the CS group was significantly increased. Conclusion Chronic exposure to tobacco smoke alone induced COPD mouse models with depression.