Thrombolysis of embolic stroke in the rat was measured using diffusion (DWI)-, T₂ (T₂WI)-, and perfusion (PWI)-weighted magnetic resonance imaging (MRI). An embolus was placed at the origin of the middle cerebral artery (MCA) by injection of an autologous single blood clot via an intraluminal catheter placed in the intracranial segment of internal carotid artery. Rats were treated with a recombinant tissue plasminogen activator (rt-PA) 1 hour after embolization (n = 9) or were not treated (n = 15). Diffusion-weighted imaging, T₂WI, and PWI were performed before, during, and after embolization from 1 hour to 7 days. After embolization in both rt-PA-treated and control animals, the apparent diffusion coefficient of water (ADC_w) and cerebral blood flow (CBF) in the ischemic region significantly declined from the preischemic control values (P < 0.001). However, mean CBF and ADC_w in the rt-PA—treated group was elevated early after administration of rt-PA compared with the untreated control group, and significant differences between the two groups were detected in CBF (24 hours after embolization, P < 0.05) and ADC_w (3, 4, and 24 hours after embolization, P < 0.05). T₂ values maximized at 24 (control group, P < 0.001) or 48 hours (treated group, P < 0.01) after embolization. The increase in T₂ in the control group was significantly higher at 24 hours and 168 hours than in the rt-PA—treated group (P < 0.05). Significant correlations (r ≥ 0.80, P < 0.05) were found between lesion volume measured 1 week after embolization and CBF and ADC_w obtained 1 hour after injection of rt-PA. Within a coronal section of brain, MRI cluster analysis, which combines ADC_w and T₂ data maps, indicated a significant reduction (P < 0.05) in the lesion 24 hours after thrombolysis compared with nontreated animals. These data demonstrate that the values for CBF and ADC_w obtained 1 hour after injection of rt-PA correlate with histologic outcome in the tissue, and that the beneficial effect of thrombolysis of an intracranial embolus by means of rt-PA is reflected in an increase of CBF and ADC_w, a reduction in the increase of T₂, and a reduction of the ischemic lesion size measured using MRI cluster analysis.