Ischemic stroke occurs most often in the territory of the middle cerebral artery (MCA) in humans. Since its description in rats more than two decades ago, the minimally invasive intraluminal suture occlusion of MCA is an increasingly used model of stroke in both rats and mice due to its ease of inducing ischemia and achieving reperfusion under well-controlled conditions. This method can be used under the guidance of laser-Doppler flowmetry to ascertain the magnitude of occlusion or reperfusion and to decrease the rate of subarachnoid hemorrhage. Ninety minutes of transient ischemia in the territory of MCA results in substantial and reproducible ischemic lesions in both the striatum and the cortex, with characteristics of lesion core and penumbra. Thus, this model is applicable to neuroprotective drug studies, including ischemic brain lesion evaluation (either in vivo with magnetic resonance imaging or post-mortem with brain tissue staining) and neurological status (motor deficits simply assessed by a six-point neurological score scale) as outcome parameters.