A Chinese medicinal formula was prepared by combining extracts from Astragalus, Siberian ginseng, wild Yam, grape seed, and wild Jujube and assessed for the protective effect of the Fangfu formula powder on the spleen of radiation-injured mice. The mice were irradiated with a one-time ⁶⁰Co γ ray 6.5 Gy dose exposure. The experimental mice were randomized into five equal groups: the control, the model , and the low, middle, and high-dose group (500 mg/kg, 1 000 mg/kg, 2 000 mg/kg, respectively). Changes in the spleen index, pathomorphisms in the spleen tissues, Caspase-3, Caspase-9, cytochrome C, CD4⁺, CD8⁺, the apoptosis-related proteins Bax, Bcl-2, and P53 protein expression, and the cell DNA damage in each group were measured. Compared with the model group, there was an increase in the body weight and spleen index of the dosed mice, with the most significant (p<0.01 or p<0.05) increase occurring in the middle- and high-dose groups. Furthermore, the Fangfu formula significantly (p<0.01 or p<0.05) increased the CD4⁺, CD8⁺, CD4⁺/CD8⁺ percentages, and Bcl-2 protein expression and reduced the level of Caspase-3, Caspase-9, cytochrome C, Tail DNA%, Tail length, olive tail moment (OTM), Bax, and P53 protein expression in spleen tissue when compared with the model group. The histopathologic examination showed that the red and white pulp area of the spleen of the dosed mice was clear, and both lymphocyte necrosis and neutrophil infiltration were decreased significantly in the dosed mice as compared to that in the model group. The data suggest that the Fangfu Formula has a protective effect on the spleen of irradiated mice. These findings might be related to inhibition of DNA damage and apoptosis.