OBJECTIVE: To establish a long-term immunosuppressive rat model for immunomodulator long-term pharmacodynamic evaluation (1 month). METHODS: Wistar rats were selected as experimental animal and cyclophosphamide (CTX) was selected as an inducer. Rats were randomly divided into normal control group, model group and treatment group, with 5 rats in each group. Model group was given 35 mg/kg CTX intraperitoneally for consecutive 3 d, and then given same dose once a week to induce model, 3 times in total, for 31 d. Normal control group was not given any treatment. Treatment group was additionally given Thymopentin (TP5) injection 1 mg/kg at third day after modeling, every other day, till the end of experiment, on the basis of model group. The changes of mental status and body weight were observed during the whole experimental period. Blood samples were collected at 4th, 11th, 18th, 25th, 32th day, and CD4+/CD8+ ratio of peripheral blood was determined. Rats were sacrificed after experiment, and thymus index and spleen index were measured. RESULTS: Compared with normal control group, mental state of the rats in the model group was poor and the body weight increased slowly; CD4+/CD8+ ratio at different time points and thymus index after experiment were decreased significantly in model group, while spleen index increased significantly, with statistical significance (P<0.05). Compared with model group, mental state of the rats and the increase of body weight were all improved in treatment group. CD4+/CD8+ ratio at 11th, 25th, 32th day and thymus index after experiment were increased significantly, while spleen index was decreased significantly, with statistical significance (P<0.05). CONCLUSIONS: The long-term immunosuppressive rat model is established successfully. The immunosuppressive level of the model is middle, and it can be used for pharmacodynamic evaluation of immunomodulator within 1 month.