Obesity is associated with increased cardiovascular mortality and morbidity mainly through insulin resistance. Dysregulation of protein secretion by adipose tissue is involved in obesity-related diseases. Adipose tissue contributes to create a subinflammatory status which could explain the disturbances in the haemostatic and fibrinolytic systems observed in obesity. Elevated plasma levels of PAI-1 demonstrated the strongest association with the degree of insulin resistance and could be an underlying mechanism for the thrombotic tendency and the progression of atherothrombosis during obesity. The effect of PAI-1 was examined on adipose tissue growth in several mouse models as well as on adipocyte differentiation in vitro. Most of the data indicate that PAI-1 can effectively modulate weight gain and may be a potential therapeutic target for controlling cardiovascular morbidity in obese subjects.