Abstract: OBJECTIVE To establish the mice model of chronic obstructive pulmonary disease (COPD) complicated with depression induced by smoke， and to evaluate the therapeutic effects and mechanism of modified Wendan Decoction on these mice models. METHODS Mice were randomly divided into normal control group and model group. Model group was given smoke four times a day. After 15 weeks， sugar consumption of both the model group and the control group were tested as well as the pathological changes of airway and lung tissue of the two groups were observed. In recognition of COPD with depression models being successfully constructed， mice in the model group were further randomly divided into model group， high dose group of Modified Wendan Decoction， low dose group of Modified Wendan Decoction and positive drug group， with the medicine administration lasting for 3 weeks. Then the sugar consumption， tail suspension test， pulmonary function and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) of each group were tested and the airway and lung tissue pathological changes were once more observed. RESULTS Compared with normal control group， the weight and sugar consumption of model group decreased and the enhanced respiratory pause (Penh) increased after 15 weeks of smoking. Compared with the model group， the body weight and sugar consumption of the Modified Wendan Decoction group increased， with significantly reduced inspiratory resistance (RI)， increased lung dynamic compliance (Cdyn)， decreased total number of leukocyte and neutrophils than those of the model group. In addition， the bronchoalveolar lavage fluid and inflammatory factors in hippocampus were decreased. CONCLUSION The COPD with depression mouse model established by smoke is in accordance with the disease development and and its clinical features. Chinese medicine Modified Wendan Decoction has therapeutic effects on the improvement of pathological and functional changes in mice with COPD and depression.