Objective To investigate the effect of chronic restraint stress on sociability in mice. Method Chronic restraint stress was applied to establish stress depression model. The mice were individually housing and restrained for 4 h per day in a 50 mL polypropylene conical tube with ventilation holes. This daily restraint was repeated for 35 consecutive days. The sucrose preference test was applied to evaluate the model. The social approach-avoidance test was used to assess the effect of chronic restraint stress on sociability. Results The sucrose intake was significantly reduced in chronic restraint stress model compared with the control mice (P < 0.01). The control group investigated the social stimulus (stranger cage)significantly longer than the object stimulus(empty cage), thereby demonstrating normal social preference. The model group showed a decrease (sniffing time and frequency)in social investigation (P < 0.05,P < 0.01, vs the control group). The chronic restraint stress group did not demonstrate social preference. The preference index in chronic restraint stress model (ratio time sniffing stranger vs. empty cage) was significantly lower compared with the control mice (P < 0.01). Conclusion The chronic restraint stress showed social avoidance in sociability test.