Objective To explore the changes of endostatin (a strong anti-angiogenesis factor) and vascular endothelial growth factor (VEGF) in the brain tissues of rabbits following cerebral ischemia induced by middle cerebral artery occlusion (MCAO). Methods Twenty-four New Zealand white rabbits were randomly divided into 5 groups: control (n = 5), sham-operation (n = 4), 2-hour ischemia (n = 5), 24-hour ischemia (n = 5), and 48-hour ischemia (n = 5). The expression of VEGF and endostatin were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. In situ hybridization was used to characterize the expression of mRNA for the endostatin. Results Both the protein (at least 50%, P 〈 0.01) and mRNA (at least 70%, P 〈 0.05) of endostatin increased significantly in the ischemic brain tissues after MCAO compared with the control group. VEGF increased at least 270% in the brain after cerebral ischemia (P 〈 0.05). Conclusion Cerebral ischemia leads to an up-regulation of endostatin in the brain, which is not associated with the increase of VEGF in the brain. The increase of endostatin may serve as a deleterious mechanism for ischemic injury through blocking angiogenesis.