We investigated microvascular damage in areas with magnetic resonance imaging (MRI)-defined apparent diffusion coefficient reduction (ADC-R) in a rat model of thromboembolic occlusion of the middle cerebral artery. Rats received either intracarotid recombinant tissue plasminogen activator (rt-PA) or saline. Microvascular basal lamina damage was quantified by immunohistochemical staining of collagen type IV and by videoimaging analysis. ADC-R positive basal ganglia (cortical) areas showed a significant reduction of stained microvascular area by 15+/-6% (8+/-7%) and the microvascular density by 13+/-5% (8+/-6%) of that on the non-ischemic control side (P<0.001). There were no significant microvascular differences between rats given rt-PA or saline, or between those with or without angiographically proven recanalization. This study reports for the first time that microvascular basal lamina damage in experimental thromboembolic stroke is confined to regions with ADC-R in MRI.