Retinal neovascularization is one of the leading causes for complete blindness in a number of diseases around the world. Endostar, a recently introduced recombinant human endostatin, has been considered as one of the most valuable anti-angiogenic agents. In this study, we demonstrate that Endostar inhibits both the proliferation of the choroid-retinal endothelial cells through limiting the progression of the cell cycle and their migration. Furthermore, Endostar induces the expression of the pigment epithelial-derived factor (PEDF) and suppresses the expression of the vascular endothelial growth factor (VEGF) and the fibroblast growth factor (FGF). Endostar also reduces the expression of the inflammatory mediator tumor necrosis factor-α (TNF-α), matrix metalloproteinases (MMPs) and vascular cell adhesion molecule-1 (VCAM-1). These findings reveal an integrated role of Endostar in the program of retinal vascular control and highlight its significant potential for broad clinical application.