OBJECTIVE: The purpose of this study was to investigated whether pretreated with Atorvastatin be helpful in diabetic or wild-type mice, and clarify the possible mechanisms. METHODS: C57/B6 and ob/ob mice treated with atorvastatin or not were subjected to middle cerebral artery occlusion (MCAO), which were killed after 2h of occlusion following by 22h of reperfusion. We used Neurological Severity Scores (NSS) to assess the severity of brain injury, and TTC staining was used to measure the infraction volume. Protein levels of PGC-1α, vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), Bcl2, Bax and signaling pathway protein of mitogen-activated protein kinase (MAPK) were estimated by western blot. RESULTS: Atorvastatin could slake the cerebral ischemic/ reperfusion injury in ob/ob diabetic mice, but do nothing on wild-type mice. The expression of PGC-1α and related angiogenic factors such as VEGF and Ang-1 were lower in the diabetic mice after MCAO than wild-type, which could be effective reversed by atorvastatin pretreatment before MCAO. This may be one of the possible mechanisms for atorvastatin to alleviate ischemic injury. MAPK pathway and apoptosis-related proteins were also involved in this course. CONCLUSION: Impaired angiogenesis mediated by PGC-1α plays an important role in exacerbating ischemic cerebral insults in diabetic mice, and pretreatment with atorvastatin before MCAO has a protective effect through the regulation of PGC-1α and angiogenic factors.