Objective Three different method were used to establish rat models of psycho-cardiac disease(comorbidity of depression and cardiovascular disease). The characteristic changes in depressive behaviors, cardiac function, and related biochemical indicators were compared to provide a choice of relevant models for psycho-cardiac disease research. Methods Sixty male Sprague-Dawley rats were randomly divided into four groups. Rats in the control group were fed without special treatment; the ISO + CUMS group was intraperitoneally injected with isoproterenol and then subjected to chronic unpredictable mild stress for 4 weeks; the LAD + CRS group underwent left anterior descending coronary artery suture ligation surgery followed by chronic restraint stress for 4 weeks; the CORT group was given corticosterone aqueous solution (10 mg/ day) for 4 weeks. The depressive-like behavior of animals was evaluated in behavioral tests. Brain-derived neurotrophic factor levels in the hippocampus were analyzed by ELISA. Plasma corticosterone levels were determined by radioimmunoassay. Cardiac function was evaluated by ultrasound. Glucocorticoid receptor levels in myocardial tissue were determined by western blot. Masson staining was utilized to assess rat myocardial tissue fibrosis. Results All three modeling method successfully induced depressive-like symptoms and showed changes in cardiac structure and cardiac function compared with the control group. The ISO + CUMS and LAD + CRS groups showed more obvious cardiac structural changes and decreased cardiac function than the CORT group. Animals in the CORT group had higher levels of circulating corticosterone. Conclusions Corticosterone administration induces an effective and simple psycho-cardiac model with obvious hypothalamic-pituitary-adrenal axis dysfunction. Isoprenaline administration plus chronic unpredictable mild stress and coronary artery suture ligation surgery plus chronic restraint stress induced more obvious changes in cardiac function. This study provides a reference for the selection of animal models for studies into the mechanisms of psycho-cardiac disease, drug screening, and pharmacodynamic evaluation.