Summary Objective: Investigation of the biophysical changes of a new rat model of cerebral artery thrombotic stroke in rat with or without thrombolytic treatment using diffusion- (DWI) and perfusion- (PWI) weighted MR imaging. Setting: Henry Ford Health Sciences Center, Detroit, MI, USA. Materials and Methods: A thrombus was induced at the origin of the middle cerebral artery (MCA) by injection of thrombin via an intraluminal catheter placed in the intracranial segment of internal carotid artery. Rats were treated with a recombinant tissue plasminogen activator (rt-PA) ( n = 8) or were untreated ( n = 10). DWI and PWI were performed before, during and after induction of thrombosis from 1 h to 7 days. Results: After onset of thrombosis in both rt-PA treated and control animals, the apparent diffusion coefficient of water (ADC w) and cerebral blood flow (CBF) values in the ischemic region significantly declined from the preischemic control ADC w and CBF values ( P < 0.01). However, mean CBF in the rt-PA treated group was elevated at 4 h of thrombosis compared to the untreated control group and a significant difference in CBF between the two groups was detected at 48 h after thrombosis ( P < 0.05). Conclusion: These data support the application of magnetic resonance imaging (MRI) to a model of cerebral thrombosis, and demonstrate that DWI and PWI provide real time and dynamic data on the evolution of a thrombotic cerebral lesion with and without thrombolysis.