The blood-retinal barrier (BRB) is essential for the normal structural and functional integrity of the retina. As the BRB serves critical functions in the eye, the BRB breakdown followed by retinal or choroidal neovascularization could therefore result in the serious vision loss. In the retina, hypoxic-ischemic stress appears to be an important cause of BRB breakdown. In particular, retinal ischemia leads to inner BRB breakdown, which is characterized by vascular leakage due to increased vascular permeability. Vascular endothelial growth factor (VEGF), the best known pro-angiogenic factor, is originally isolated as a vascular permeability factor to increase the vascular permeability of microvessels via uncoupling of junctional molecules in endothelial cells. It has been known that VEGF, sufficient to induce vascular abnormalities including vascular leakage, microangiopathy, and neovascularization plays a major role in the initiation and development of variable retinopathies. That is, VEGF-mediated alteration of tight junction proteins leads to BRB breakdown which result in retinal neovascularization. Actually, with recent development of anti-VEGF therapy using anti-VEGF antibody, the visual outcome in patients with retinal and choroidal vascular diseases has been revolutionarily improved. Based on my recent results, I’d like to suggest that targeting to VEGF-mediated BRB breakdown could be a therapeutic strategy to diabetic retinopathy.