Endostatin (ES), the C-terminal fragment of collagen XVIII, is a potent angiogenesis inhibitor. At present, there are a large number of research papers on ES. It has already been on clinical stage Ⅱ and been widely used in inhibition of neovascularization (NV). However, how to improve the bioactivity of ES is still a matter of ongoing discussion. The objective of this review is to elucidate the relationship between the modified ES and ocular neovascualrization, and to discuss the superiority based on the structure modification. The structure can be changed either by covalent modification or by genetic mutation. It is proposed that the secondary structral ES enhance the anti-angiogenic activity. Studies on modified ES also shed light on our understanding of the molecular action mechanisms of ES. Modified ES may be exploited as a new angiogenesis inhibitor for therapeutic applications, in substitution of the native ES.