To test the hypothesis that combination treatment of embolic stroke with rtPA and statins improves the efficacy of thrombolytic therapy in rats. Rats subjected to embolic MCA occlusion (MCAo) were randomized into control (n = 10) and treatment (n = 9) groups. Four hours after MCAo, a combination of rtPA and atorvastatin (treatment) or saline (control) was administered. MRI measurements were performed on all animals at 2 h, 24 h and 48 h after MCAo. The patency of cerebral microvessels was examined using fluorescent microscopy. MRI images showed complete blockage of the right MCA and a reduction of CBF in the territory supplied by the MCA 2 h after MCAo for all animals. By 48 h after stroke, MRI showed that the decreased lesion size, elevated CBF and increased incidence of recanalization were found in treated rats compared with the control rats. The combination treatment significantly increased microvascular patency (16.3 +/- 5.5% vs. 12.4 +/- 3.5%, of field-of-view) and reduced the infarct volume (23.1 +/- 9.6% vs. 38.8 +/- 13.3%, of hemisphere). These data demonstrate that the co-administration of rtPA and atorvastatin 4 h after ischemia is efficacious and is reflected by the MRI indices of recanalization of the MCA, reduction of secondary microvascular perfusion deficits and reduction of the ischemic lesion.