Thrombolytic agents positively resolve existing thrombi by accelerating the activity of plasmin, a key enzyme of the fibrinolytic pathway. The main drug in use is a plasminogen activator (PA) which degrades plasminogen to plasmin. PA is classified into urokinase-type (u-PA) and tissue-type (t-PA). Because t-PA more selectively activates plasmin onto the surface of thrombi, it induces less in terms of systemic hemorrhagic complications. Beside the main effects, some articles have reported that t-PA causes damage to blood brain barrier structures and has a level of neuron toxicity. With this, delayed administration of t-PA for acute ischemic stroke may accelerate ischemic damage of brain tissue. In circulating blood, plasmin itself is rapidly inactivated by a plasmin-inhibitor, so with this, intra-arterial administration of plasmin directly near thrombi site is currently under investigation.