Glycocalyx (GC) is represented by protein-polysaccharide compounds lining the inner surface of endothelial cells in the form of a gel. GC plays an important role in the regulation of vascular homeostasis, controls vascular wall permeability and microvascular tone, prevents microvascular thrombosis and participates in the regulation of leukocyte adhesion. Damage of endothelial HA is a part and initial link of pathophysiological processes underlying the development of complications of diabetes mellitus (DM). In most cases of DM is accompanied by degradation of HA caused by hyperglycemia, which leads to impaired microcirculatory perfusion and organ dysfunction. Further study of HA, determination of its contribution to the development of diabetes complications is a very promising area of research. In this review, we analyze the main mechanisms of destruction and the role of HA in the pathophysiological mechanisms of the development of DM complications. Although numerous studies indicate a significant role of HA dysfunction in the development of micro- and macroangiopathies in the outcome of diabetes, many aspects of pathophysiological processes are still unexplored and require further research.