The insulin resistance syndrome (IRS) with obesity is large-word wide-spread and represents a strong risk factor for vascular disease. Atherothrombotic complications in IRS are partly attributed to a dysregulation of hemostasis inducing a prothrombotic state which includes endothelial activation, hyperactivity of platelets, hypercoagulability and hypofibrinolysis. This latter, due to elevated PAI-1 levels, is a core feature of the IRS. Most of the prothrombotic modifications can be reversed by loosing weight. Low grade inflammation with prolonged cytokines mediated acute phase reaction is actually considered as strongly related to the IRS and is involved in the dysregulation of hemostasis. TNF pathway and TGFb play an important role in the regulation of PAI-1 synthesis in the adipose tissue and the liver with steatosis. Interestingly, modulation of PAI-1 expression in adipose tissue influences adipose tissue growth, increasing once more the spectrum of the non hemostatic functions of coagulation/fibrinolysis parameters.