In recent years, evidence has been accumulating that tissue plasminogen activator (tPA) possesses neurotoxic effects. However, such deleterious effects have been attributed to endogenously generated tPA. In the present study, focusing on exogenously administered tPA for the purpose of fibrinolysis, we evaluated the extent and the degree of extravasated tPA in a rat model of thromboembolic stroke. Even after early recanalization of occluded cerebral vessels, significant infiltration of tPA occurred through the cerebral vessels. It is assumed that exogenous tPA also exerts neurotoxic effects in the ischemic brain tissue.