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Purpose: To examine the effect of an intravitreal injection of angiostatin on vascular leakage in retina and iris of the diabetes and study its possible mechanism.Methods: Experimental diabetes was induced in 24 rats by an intravenous injection of streptozotocin (STZ) during 48 adult rats. Three groups were randomization distributed of them. There were 8 of both normal and diabetic rats in each group. STZ-diabetic rats and age-matched normal rats received an intravitreal injection of 5 μl of sterile PBS (Phosphate Buffered Saline) into the right eye, and the left eye was non-injected in the group A; Angiostatin was injected into the vitreous of the right eye (7.5 μg/5μl/eye), and the left eye received the same volume of sterile PBS as the control in the group B and C. The vascular permeability of retina and iris was measured using the Evans blue method at 2 days following the injection in the group A and B. Expres sion of VEGF in retina was evaluated using western blot analysis 24 hours following the injection in the group C.Results: Diabetic rats showed significant increases of vascular permeability in the retina (P＜0.01) and iris (P＜0.05). Angiostatin-injected eyes showed significant decreases in vascular permeability in the retina (P＜0.01) and iris (P＜0.05) comparing with the PBS-injected eyes in STZ-diabetic rats. In contrast, intravitreal injection of the same dose of angiostatin into the age-matched normal rats did not result in any significant reduction in vascular permeability in the retina and iris, when compared with the contralateral eye with PBS injection (P＞0.05). Angiostatin injection significantly reduced VEGF level in the retinas of STZ-diabetic rats but did not affect retinal VEGF level in normal rats.Conclusions: Angiostatin significantly reduce pathological vascular permeability in the retina and iris of STZ-diabetic rats but not in normal rats. Angiostatin down-regulates VEGF expression and thus, blocks the major cause of vascular leakage in the diabetic retina. Therefore, angiostatin may have a therapeutic potential in the treatment of diabetic macular edema, cystoid macular edema, uvietis and other diseases with vascular leakage.