Objective To investigate the effects of depression-like behavior induced by chronic restraint stress (CRS) on pulmonary function in mice and the underlying mechanisms. Methods Twenty-four C57BL/6J mice were randomly divided into three groups: normal group, depression group, and respiratory disease group. The depression group was established by CRS. Behavioral tests, pulmonary function, spleen index, adrenal gland index, lung and hippocampal histopathology, serum inflammatory cytokines, and hippocampal Ezrin expression were evaluated. Results Compared with normal mice, the depressed mice showed increased airway resistance (P<0.01) and decreased lung compliance (P<0.01); spleen index and adrenal gland index were elevated (P<0.01). Adrenal gland index was positively correlated with airway resistance (r=0.764, P<0.01) and negatively correlated with lung compliance (r=-0.614, P<0.01). The proportion of degenerating neurons in the hippocampus was significantly higher (P<0.01). Serum IL-1β was elevated (P<0.01). Hippocampal Ezrin expression was decreased (P<0.01), and correlation analysis revealed a significant negative correlation between hippocampal Ezrin expression and adrenal gland index (r=-0.633, P<0.01). Conclusions CRS-induced depression-like behavior in mice can lead to increased airway resistance and reduced lung compliance, and this effect may be mediated by the adrenal glands.