The aim of early thrombolytic therapy in acute stroke is to obtain early recanalization of occluded cerebral arteries and prevent or reduce irreversible ischemic brain damage. In this study, Seldinger technique and digital subtraction angiography were used to verify thromboembolic occlusion of the common carotid artery by an autologous 12-hour-old thrombus in 28 rabbits. Thirty minutes after embolization, 2 mg/kg of recombinant tissue-plasminogen activator (rt-PA) was delivered intravenously by way of the femoral vein in group A (n = 8) and through a local intra-arterial infusion in group B (n = 8). Twelve control animals received an equivalent volume of saline intravenously (group C, n = 6) or by local intra-arterial infusion (group D, n = 6). A comparison of posttreatment angiographs of the treatment groups and the control groups was used to demonstrate reperfusion induced by thrombolytic therapy. None of the control animals showed any evidence of recanalization. Both intravenously (group A) and intra-arterially (group B) treated animals achieved 100% recanalization, although the average time to recanalization was significantly longer in group A (P = .01; 123.7 vs 82.5 min). These results suggest that local intra-arterial administration of rt-PA within 30 minutes produces more rapid reperfusion compared with the intravenous route. Further studies and additional treatments are needed to widen the therapeutic window and decrease hemorrhagic side effects.