Insulin is essential to the physiological regulation of high density lipoprotein (HDL) cholesterol metabolism. It acts directly at the hepatic level by favouring HDL2 to HDL3 conversion (by its action on hepatic lipase). In the peripheral circulation, it induces HDL2 formation by allowing triglyceride-rich lipoprotein catabolism by lipoprotein lipase (LPL) and free cholesterol esterification by lecithin acyl cholesterol transferase (LCAT). In the case of insulin deficiency or peripheral insulin resistance, there is a reduction of HDL cholesterol related to HDL2 decrease, partly due to LPL deficiency. In the case of endogenous hyperinsulinism, there is an intrahepatic disturbance of HDL metabolism partly related to excessive synthesis of VLDL-TG and leading to the decrease of HDL2/HDL3 and enhanced formation of HDL2 TG. When hepatic hyperinsulinism is associated with peripheral insulin resistance, HDL cholesterol decrease is the consequence of both intrahepatic action of insulin and diminution of its peripheric action. Optimized insulin therapy can normalize HDL cholesterol in case of true insulin deficiency. When there is preservation of insulin secretion, HDL cholesterol remains lower than controls. Insulinopenia as well as hyperinsulinism can favour atherogenic lipoprotein disturbances.