Objective To investigate changes of the pathological behaviors and core markers in BALB/ c mice treated by 4T1 inflammatory breast cancer cells inoculation and corticosterone injection. Methods Breast cancer mouse mod els were established by inoculation of 4T1 inflammatory breast cancer cells and randomly divided into two groups: breast cancer and breast cancer with corticosterone groups. Healthy mice were randomly divided into two groups: normal control and depression groups. Subsequently, corticosterone injections (30 mg/ kg, 21 days) were administered to the depression and breast cancer with corticosterone groups. At the end of the experiment, depression-like behaviors of mice in each group were assessed by sugared water consumption, open field, and novel feeding tests. Then, all the mice were sacrificed by decapitation, and the tumor weight and volume in each mouse were measured. The levels of tumor antigens carbohydrate antigen (CA) 153, CA125, carcinoembryonic antigen (CEA), and 5-hydroxytryptamine (5-HT), dopamine(DA), norepinephrine (NE) were detected by ELISA. Results In the breast cancer with corticosterone group, the tumor weight and volume were increased significantly, and the levels of CA153, CA125, and CEA were increased significantly. Furthermore, the degree of sugar-water bias was reduced significantly, and the desire to explore the environment was weakened in the breast cancer mouse with corticosterone group. The concentrations of 5-HT, DA, and NE were reduced significantly. Conclusions After corticosterone treatment, breast cancer-bearing mice exhibit obvious depression-like behaviors. Neurotransmitters, breast cancer markers, and tumors are also changed. Based on the above indicators, this method of 4T1 inflammatory breast cancer cell inoculation combined with corticosterone injection can generate mouse model of breast cancer complicated with depression, which provides a reference for animal depression experiments.