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Diabetic retinopathy (DR) is one of the most prevalent microvascular complications of diabetes, and the most leading cause of visual loss around the world. The lack of effective and approved treatment in DR is a major challenge for diabetic patients. Nowadays, natural compounds have got attention of the researchers for management of DR. Many evidences suggest that puerarin as a natural polyphenol exerts advantageous effects against DR. In the present review, we summarized the protective effects of puerarin against DR, and discussed the underlying mechanisms of these effects. Puerarin attenuates retinal neovascularization and neurodegeneration in diabetes mellitus, and the underlying mechanisms are related to antioxidant, anti-inflammatory, and antiapoptotic properties of the compound. In conclusion, puerarin might be a potential adjuvant agent for the prevention and treatment of DR. However, comprehensive studies are necessary to show its effectiveness and safety, particularly in human.