Abstract: The aims of the present study were to observe the immunosuppression effect of cyclophosphamide with different dosage regimen on mice and to explore the method for establishing immunosuppression model induced by cyclophosphamide in mice. Single or multiple doses of cyclophosphamide were intraperitoneally injected in mice. The immune organ index, serous level of alanine aminotransferase, aspartate aminotransferase, urea nitrogen and creatinine, blood leukocyte count, and splenic lymphocyte transformation were determined to evaluate the effect of cyclophosphamide on immunity and hepatic and renal function of mice. The results showed that both the multiple administration of 10, 20, 30, 40 mg/ （kg·BW） of cyclophosphamide for consecutive seven days respectively and single administration of 150 mg/ （kg·BW） of cyclophosphamide exhibited immunosuppression effect on mice and caused the changes of indicators associated with hepatic and renal function;the immunosuppression effect produced by multiple administration with lower dosage of cyclophosphamide was superior to that produced by single administration with higher dosage, and the immunosuppression effect was improved with the increase of dosage under multiple administration mode. The combined data suggest that the immunosuppression model in mice can be established by multiple administration of 30-40 mg/（kg·BW） of cyclophosphamide for consecutive seven days.