Insulin resistance and the defect of insulin secretion are two basic pathogenic mechanisms in the development of type 2 diabetes mellitus. The presence both of these defects is necessary for clinical manifestation of type 2 diabetes mellitus. Due to progressive loss of function and number of B-cells insulin secretion is declined. Insulin resistance, if it is not intervened, remains unchanged in the course of the disease, so gradual increasing of fasting and postprandial glycemias is clear outcome of relative and later also absolute deficiency of insulin. Exact causes of defect of insulin secretion in the course of type 2 diabetes mellitus are not completely known. A number of factors have been posited to contribute to the decline of insulin secretion. These include: genetic factors, glukotoxicity, lipotoxicity, oxidative stress, defects of secretion of glukagone like peptid (GLP-1), amyloidosis, increased apoptosis of B-cells.