Diabetes retinopathy(DR)may continue to develop even if blood sugar is well controlled, which indicates that previous hyperglycemia will lead to long-term harmful vascular dysfunction, and this phenomenon is defined as “metabolic memory” of diabetes retinopathy. Because the onset of DR is insidious, clinical symptomatic treatment is mainly used. Effective means of early diagnosis, accurate treatment and prognosis are lacking and new diagnosis and treatment ideas need to be developed urgently. In recent years, many new studies have shown that epigenetic modification is involved in the pathogenesis of DR “metabolic memory” in DNA methylation, histone post-translational modification and microRNA(microRNAs,miRNAs)regulation, which provides a direction and strategy for the exploration of DR molecular mechanism. In this review, we discussed the role of epigenetic modification in the pathogenesis of DR and analyzed the challenges and prospects of its application in the treatment of DR, with a view to provide a reference for early diagnosis and treatment of DR in the future.