In the present study, human umbilical vein endothelial cells (HUVECs) treated with different concentrations of glucose and a streptozocin-induced rat DM model were used to investigate the role of IRSp53 in hyperglycemia-induced endothelial dysfunction, the relationship between IRSp53 and gal-3, and the effect of insulin on hyperglycemia-induced endothelial dysfunction. Here, LGALS3 is linked to diabetes mellitus.