We examined a protective effect of anti-P-selectin monoclonal antibody against rat ischemic brain injury with 24 h of middle cerebral artery occlusion (MCAO). Anti-rat P-selectin monoclonal antibody, was intravenously injected at a dose of 1 mg/kg at 5 min before MCAO. Control animals received the same volume of vehicle. MCAO was accomplished by an insertion of nylon thread with silicone coating for 24 h. Application of anti-P-selectin antibody significantly reduced infarct size and brain water content at 24 h of MCAO. Although leukocyte infiltration was not normally detected, it became remarkably evident at 1 day of MCAO. However, treatment with ARP 2-4 significantly reduced the number of leukocytes. These results demonstrated that administration of monoclonal antibody against P-selectin attenuated infarct size and brain edema, which was associated with reduction of leukocyte infiltration.