Acute cerebral ischemia is associated with an increased extracellular dopamine accumulation. Attenuation or prevention of excessive dopamine accumulation alleviates the cerebral ischemic damage. Propofol, an intravenous anesthetic, has been suggested to have neuroprotective properties. The effect of propofol on dopaminergic neurotransmitters is unclear. The in vivo microdialysis technique was used in this study to examine the effect of propofol on infarct size and striatal dopamine accumulation in rat model of temporary middle cerebral artery occlusion. Sixteen rats were fitted with a right striatal microdialysis probe. Ischemia was induced by inserting a 4-0 monofilament nylon suture into the middle cerebral artery. Propofol was intravenously infused in eight rats during ischemia (60 min) and reperfusion (60 min) at an average dose of 36 mg/kg/h. Control rats (n=8) received vehicle infusion. The infarct size was determined at the end of the experiment. Propofol significantly reduced infarct size, the median (interquatile range) value was 6.84% (7.68%), significantly lower than that in the control group, which was 28.04% (32.28%) (p<0.01). The middle cerebral artery occlusion significantly increased dopamine accumulation in the striatum. Propofol infusion significantly attenuated this middle cerebral artery occlusion-induced dopamine accumulation. The data demonstrate that propofol, when administered during ischemia and reperfusion, provides neuroprotection in our middle cerebral artery occlusion in rat model. The data also suggest that attenuated dopamine accumulation may be one of the factors contributing to the neuroprotective property of propofol.