Focal cerebral ischemia is a cause of stroke in infants. Current neonatal rodent models, however, require a combination of unilateral carotid artery ligation and exposure to systemic hypoxia, thus limiting the understanding of the pathophysiology of focal neonatal cerebral ischemia. Our aim was to develop a model of reproducible non-hemorrhagic focal ischemia-reperfusion in the neonate using transient middle cerebral artery (MCA) occlusion in P7 rats. Right common carotid artery was exposed and the right external carotid ligated in 16 rat pups. A coated nylon filament (#7) was advanced for 8 mm through an incision in external carotid artery occluding the MCA. The filament was then sutured and pups were returned to the dams. After three hours, diffusion-weighted imaging (DWI) was performed, and reperfusion was achieved by removal of the suture filament. At 24 hours, pups were perfused through the heart with 2% TTC. Brains were removed, fixed in 4% buffered paraformaldehyde, and cut into 4 or 5 coronal slices. The size of areas of moderate-to-complete TTC discoloration unilateral to MCA occlusion was determined serially using computer-assisted image analysis. Based on DWI performed during MCA occlusion, cytotoxic edema was evident in MCA distribution ipsilateral to the occlusion. Infarcts were seen in 15 animals and included 38.7±13.6%(mean±SD) of ischemic hemisphere. Hemorrhage was observed in one rat. This ischemia-reperfusion model will allow further study of the susceptibility of the newborn brain to ischemic insult during development.