Ephrin-B2 has been shown to participate in angiogenesis, but the underlying mechanisms involved remain unclear. In this study, a rat model of focal cerebral ischemia was prepared by focal middle cerebral artery occlusion, followed by 24-hour reperfusion. Then, ephrin-B2 protein was administered intracerebroventricularly for 3 consecutive days via a micro-osmotic pump. West blot assay and quantitative real-time reverse transcription PCR demonstrated the expression levels of angiopoietin-1 (Ang-1) mRNA and protein in the penumbra cortex of the ephrin-B2 treated group were decreased at day 4 atfer reperfusion, and increased at day 28, while the expression levels of angiopoietin-2 (Ang-2) were highly up-regulated at all time points tested. Double immunolfuorescent staining indicated that Ang-1 and Ang-2 were both expressed in vascular endothelial cells positive for CD31. These ifndings indicate that ephrin-B2 inlfuences the expres-sions of Ang-1 and Ang-2 during angiogenesis following transient focal cerebral ischemia.