Objective To investigate the effect of focal cerebral ischemic preconditioning (IPC)on the activation of microglias to explore the endogenous neuroprotection of microglias. Methods SD rats were divided into 4 groups, in which the IPC (10 minutes)+MCAO group and SS (without IPC)+MCAO group received middle cerebral artery occlusion (MCAO, 2 h) followed by reperfusion (22 h),and the other 2 groups received SS+SS (blank controls) or IPC+SS (without MCAO). The infarct volume,ultrastructure and activation changes of microglias were evaluated in each group by riphenyltetrazolium chloride (TTC) staining, electron microscope and immunohistochemical staining, respectively. Results Compared with SS+MCAO group, the further reduction of infarct volume and slight ultrastructure changes were observed in the IPC+MCAO group. More severe pathological changes in the SS+MCAO group were observed than those in the IPC+MCAO group. In contrast with that in the IPC+SS group, the activation of microglias further increased in the SS+MCAO and IPC+MCAO group; while that in the SS+MCAO was significantly higher than that in the IPC+MCAO group (P＜0.05). Conclusion Microglias play a dual role in the induction of ischemic tolerance, and inflammation mediated by activation of microglias might be a key event in the mechanism of endogenous neuroprotection induced by focal IPC.