Objectives: This study was performed to investigate the effects of Semen Persicae (SP) on infarct volume, COX-2 protein expression in the middle cerebral artery occlusion (MCAo) rats. Methods: Twenty-eight rats were randomly assigned to four groups (MCAo experimental group, MCAo control group, sham experimental group, control group). The middle cerebral artery (MCA) was occluded in the MCAo group by proximal focal cerebral ischemia rat model, while the MCA was not occluded in the sham group. SP extraction was administrated for 4 days to each experimental group. Neuroprotective effects were investigated by measurement of brain damage using 2, 3, 5-triphenyltetrazolium chloride staining and analysis of COX-2 protein expression by western blotting. Results: The occurrence of infarct volume in the SP oral administration group decreased compared to the control group. COX-2 protein expression in the SP oral administration group decreased compared to the control group. Conclusions: The present study demonstrates the effect of SP in reducing infarct volume and decreasing COX-2 expression.