A defect in the fibrinolytic system appears to be a risk factor for the development of cardiovascular disease. Such a defect is mainly characterized by increased plasma levels of an inhibitor of fibrinolysis the plasminogen activator inhibitor 1 (PAI-1). PAI-1 levels are elevated in the common syndrome of insulin resistance as it is encountered in obese non diabetic and in non insulin dependent diabetic subjects. These levels are closely related to insulinaemia in cross sectional studies as well as in intervention studies. Although in vitro insulin stimulates the PAI-1 synthesis in hepatocyte, but not in endothelial cells, acute elevation of insulinaemia in vivo in man does not result in an increase in PAI-1 levels. The mechanisms linking insulin-resistance, insulin and PAI-1 levels in man are still not understood.