Epigenetic mechanisms influence gene expression and function without modification of the base sequence of DNA and may generateagenetic phenotype. Epigenetic modifications include DNA methylation, histone modifications, and deployment of noncoding RNA. There is growing evidence that epigenetic mechanisms could playacrucial role in the development of diabetic retinopathy (DR). Molecular biological methods which could maintain mitochondrial homeostasis through the regulation of epigenetic mechanisms may prevent the development of DR. Epigenetic-related treatment modalities will become the new direction of targeted therapy for DR.