Objective To investigate the dynamic changes of complement regulatory protein CD46 expression and discuss its possible mechanisms cerebral ischemia-reperfusion injury. Methods The middle cerebral artery occlusion (MACO) model was induced through filament method. Brain pathological injury was recorded. Immuno?uorescence and real time RT-PCR method were used to detect complement regulatory protein CD46 expression. Results Brain pathological injury was the most serious at 24h after reperfusion. The complement regulatory protein CD46 expression decreased gradually after local cerebral ischemia-reperfusion injury, to the lowest at 24h after reperfusion, and returned to normal at 96h after reperfusion. complement regulatory protein CD46 expression was negatively correlated with brain pathological injury. Conclusions The complement regulatory protein CD46 has a significant change after cerebral ischemia-reperfusion. It is speculated that it participates in the injury after ischemia-reperfusion. So regulation of complement regulatory protein CD46 is likely to be a new important method of treatment for ischemia-reperfusion injury.