Objective To investigate the effect of α-mangostin on immune function in a cyclophosphamide (CTX)-induced immunosuppressive mouse model, so as to provide experimental basis for further study of the mechanism of α-mangostin and its potential for development as a new drug to enhance immunity. Methods Mice were randomly divided into five groups: normal control group, immunosuppressive group, and high, middle, and low dose groups. All groups except the normal control group were given CTX to create the immunosuppressive model in the first 7 days. In the latter 14 days, the normal control group was given normal saline, the immunosuppressive group was given corn oil, and the three dose groups were given different doses of α-mangostin. The mice were killed 24 h after the last treatment. We assessed the effect of α-mangostin on immune function in mice by detecting delayed allergic reaction ( DTH), serum hemolysin ( HC50), macrophage phagocytosis (carbon clearance test), thymus and spleen index of immune organs, natural killer cell (NK cell) activity (MTT method ), peripheral white blood cell count, and splenic lymphocyte proliferation. Results The immunosuppressive mouse model was established by intragastric administration of CTX. After administration, the thymus and spleen index, hemolytic value, spleen lymphocyte proliferation rate and NK cell activity in immunosuppressive mice were increased by different doses of α-mangostin. The effect was most prominent in the high dose group, in which the total dose of α-mangostin was [100 mg (kg,d)^-1 ]. In many experiments, the difference was statistically significant compared with the immunosuppressive group (P< 0. 01). In the delayed allergic reaction, there was significant difference between the high dose group and the normal control group and immunosuppressive group (P< 0. 05), but there was no significant difference between the other groups (P> 0. 05). There was a significant difference in peripheral white blood cell counts between the high dose group and the immunosuppressive group (P< 0. 01), but no conspicuous difference between the other groups ( P> 0. 05 ). Macrophage phagocytosis, measured by carbon clearance assay, was similar in the immunosuppressive group and each dose group ( P> 0. 05). Conclusions mangostin had a dose-dependent regulating effect in immunosuppressed mice, and the high dose of α-mangostin demonstrated the strongest improvement of immune function in immunosuppressed mice.