Purpose: This study was done to identify whether pre-conditioning exercise has neuroprotective effects against cerebral ischemia, through enhance brain microvascular integrity. Methods: Adult male Sprague-Dawley rats were randomly divided into four groups: 1) Normal (n=10); 2) Exercise (n=10); 3) Middle cerebral artery occlusion (MCAo), n=10); 4) Exercise+MCAo (n= 10). Both exercise groups ran on a treadmill at a speed of 15 m/min, 30 min/day for 4 weeks, then, MCAo was performed for 90 min. Brain infarction was measured by Nissl staining. Examination of the remaining neuronal cell after MCAo, and microvascular protein expression on the motor cortex, showed the expression of Neuronal Nuclei (NeuN), Vascular endothelial growth factor (VEGF) & laminin. Results: After 48 hr of MCAo, the infarct volume was significantly reduced in the Ex+MCAo group ($15.6{pm}2.7%$) compared to the MCAo group ($44.9{pm}3.8%$) (p<.05), and many neuronal cells were detected in the Ex+ MCAo group ($70.8{pm}3.9%$) compared to the MCAo group ($43.4{pm}5.1%$) (p<.05). The immunoreactivity of laminin, as a marker of microvessels and Vascular endothelial growth factor (VEGF) were intensively increased in the Ex+MCAo group compared to the MCAo group. Conclusion: These findings suggest that the neuroprotective effects of exercise pre-conditioning reduce ischemic brain injury through strengthening the microvascular integrity after cerebral ischemia.