Among the molecular mechanisms of diabetic microangi- opathy development, the key is the activation of glia, which is accompanied by the formation of specific markers: S100 protein, glial fibrillary acidic protein (GFAP), and vascular endothelial growth factor (VEGF). The aim of the study was to establish the early mechanisms of diabetic microangiopathy development and the effect of cellular protein kinase blockade on it. Diabetic retinopathy was modeled in male Wistar rats by a single injection of streptozotocin (50 mg/kg). Rats were divided into 3 groups: control, with insulin injection (30 U), and with insulin and sorafenib injection (55 mg/kg. Immunohistochemical (for all markers) and immunoblotting (for GFAP) studies were performed. Ultrathin sections of the retina were examined using a PEM 125k microscope . An increase in the expression of all markers was found in the processes of Müller cells and astrocytes that formed muff-like plexuses around microaneurysms and newly formed capillaries. There was a sequence of marker activation: first, the expression of the S100 protein (astrocytic reaction) increased, then GFAP (involvement of Müller cells and reactive gliosis), and in the late period, VEGF, which caused the activation of pathological angiogenesis. Inhibi- tion of the development of microangiopathy was established when blocking cellular protein kinases with sorafenib, which was associated with the suppression of the expression of the studied markers.