Objective To explore the effects of fluoxetine on dual stress induced depressive-like and anxiety-like behaviors in Disrupted in Schizophrenia 1（ DISC1） transgenic mice. Methods Sixteen C57BL/6 wild-type mice were randomly assigned into two groups with 8 in each group， the WT-stress group and the WTcontrol group. Sixteen C57BL/6 LBD-DISC1 transgenic mice were also randomly assigned into two groups with 8 in each， the DISC1-stress group and the DISC1-control group. The WT-stress group and the DISC1-stress group received maternal separation and chronic unpredictable mild stress. All mice were treated with fluoxetine for four weeks. The sucrose consumption， the forced swim test and the open field test were used to evaluate the depressive-like and anxiety-like behaviors. Results There was no significant difference in the immobility time in the forced swim test and the migration distance in the centre area in the open field test among each group of mice after the fluoxetine treatment. The preference for sucrose solution in DISC1-stress group and body weight were still low（ P＜ 0.01）. Conclusions Fluoxetine can improve the stress induced anxiety and depression in DISC1 mice. However， it cannot alleviate anhedonia and the loss of body weight.