This review addresses the initial stages of nonproliferative diabetic retinopathy in diabetes type 2. The natural history of the initial lesions occurring in the diabetic retina has particular relevance for our understanding and management of diabetic retinal disease, one of the major causes of vision loss in the western world. Diabetic retinal lesions are still reversible at this stage opening entirely new opportunities for effective intervention. Four main alterations characterize these early stages of diabetic retinopathy: microaneurysms/hemorrhages, alteration of the blood-retinal barrier, capillary closure and alterations in the neuronal and glial cells of the retina. These alterations may be monitored by red-dot counting on eye fundus images and by fluorescein leakage and retinal thickness measurements. A combination of these methods through multimodal macula mapping has contributed by identifying three different phenotypes of diabetic retinopathy. They show different types and rates of progression which suggest the involvement of different susceptibility genes. The identification of different phenotypes opens the door for genotype characterization, different management strategies targeted treatments.