Abstract：Objective: To investigate the alterations of expressions of glial fibrillary acidic protein (GFAP) and S-100 proteins in astrocyte (AST) of cat brain prefrontal motor cortex after gamma knife irradiation, and then to choose appropriate dose, decrease adverse reaction,and provide sensitive monitoring indicators for the clinical treatment of epilepsy with gamma knife. Methods: 45 health domestic cats were randomly divided into three groups:control group, gamma knife 10Gy irradiation group and 25Gy irradiation group. Five cats were killed randomly in each group at 24h, 7d and 14d after gamma knife irradiation. The target areas were sampled and underwent. Results: The expressions of GFAP and S-100 proteins increased in AST of cat’s normal prefrontal motor cortex after gamma knife irradiation within two weeks,and correlated positively to dose and time . Conclusions: The expressions of GFAP and S-100 proteins increased in AST of cat’s normal prefrontal motor cortex after gamma knife irradiation within two weeks,and correlated positively to dose and time,which suggested that S-100 protein may be the more sensitive indicator in acute phase of radiation-induced brain injury.