The effects of the thrombin inhibitor argatroban on the number of inflammatory cells and reactive astrocytes were investigated in a rat brain injury model. Gelatin sponge soaked with thrombin inhibitor (treatment group) or saline (control group) was placed in the brain defect to assess the infiltration of inflammatory cells by hematoxylin-eosin and immunohistochemical staining. Expression of polymorphonuclear leukocytes (PMNs) and monocyte/macrophage (Mo/Mo) cells, and vimentin (VIM)-positive astrocytes and glial fibrillary acidic protein (GFAP)-positive astrocytes were compared between groups. In the treatment group, infiltration of both PMNs and Mo/Mo cells, and the number of VIM-positive astrocytes were significantly reduced, but the number of GFAP-positive astrocytes was not different from the control group. Thrombin inhibitor suppresses the infiltration of inflammatory cells and excessive gliosis caused by VIM-positive astrocytes, but not expression of GFAP-positive astrocytes, suggesting minimization of secondary brain damage and promotion of the conditions required for neural regeneration.