Insulin metabolism in erythrocytes and hepatocytes of normal and experimental diabetic rats was studied. Insulin-degrading complex of erythrocytes and hepatocytes was investigated at low insulin concentration in blood. Kinetic parameters of insulinase depend on insulin concentration in blood have shown. Thermo-acid resistant non-competitive endogenous inhibitors were purified from erythrocytes and hepatocytes. Increase of endogenous inhibitors influence insulin-degrading enzyme in diabetes. Synthesis of insulin-degrading enzyme in hepatocytes of diabetic rats was reduced. These results suggest that insulin-degrading activity in erythrocytes and hepatocytes is regulated by endogenous inhibitors, by synthesis of insulinase. This change of blood insulin concentration influences practically all the components of insulin-degrading complex.