Using magnetic resonance imaging (MRI), we investigated treatment of a rat model of embolic stroke with rt-PA via intra-arterial (IA) and intravenous (IV) routes of administration. Rats were treated with rt-PA by either IA ( n=13) or IV ( n=13) routes at 3 h after stroke induction. Diffusion, perfusion, T 2, and magnetization transfer MRI were performed prior to and at 1–3 and at 24 h after embolization. The IA treated group exhibited smaller lesion volumes than the IV treated group ( p=0.02). The relative areas with low ADC w and cerebral blood flow (CBF) after IA rt-PA intervention were significantly ( p≤0.03) smaller than those in the IV treated group at 24 h after embolization. Significant differences ( p<0.02) between IA and IV treated groups in the relative area with high T 2 and inverse of the apparent forward transfer rate of magnetization ( k inv) in the ipsilateral hemisphere were also detected at 24 h after embolization. The IA treated group exhibited less intracerebral hemorrhage (27%) than the IV treated (64%) groups. Our data suggest that the beneficial effects of IA rt-PA treatment can be detected by changes in CBF, ADC w, T 2, and k inv.