In acute ischemic stroke patients, administration of tissue plasminogen activator (tPA) was proven to improve clinical outcome. On the other hand, neurotoxic effects of tPA have been reported in animal experimental studies. Using a rat thromboembolic stroke model, we examined whether or not the free radical scavenger, edaravone, could attenuate such neurotoxic effect of tPA administered for the purpose of fibrinolysis. Even when early recanalization was induced by administering tPA at 30 minutes after the onset of ischemia, significant amount of tPA was extravasated through the cerebral vessels. Edaravone significantly attenuated extravasation of tPA. Combination therapy using tPA and edaravone appears to be a promising strategy for diminishing the negative effects of tPA.