Trombomodulin (TM) is a 557 amino acid a glycosylated transmembrane protein and is a thrombin receptor located on endothelial cell surface. It was named as thrombomodulin due to its modulator role on the functions of thrombin. While a part of TMÕs physiological functions are through the activity of the TM-trombin complex on protein C and on thrombin activated fibrinolysis inhibitor (TAFI), a substantial number TM functions are independent from thrombin. The latter includes TMÕs effects on inflammation, embryogenesis, stroke, cancer, diabetes mellitus and collagen vascular disease.Protein C is a physiological anticoagulant protein which inactivates FVa and FVIIIa, thus inhibiting excessive coagulation. Activation of Protein C is dependent on TM availability, rendering TM an important an important actor in the regulation of the coagulation and fibrinolytic cascades.TM gene polymorphisms are rare but important in the pathogenesis of some common disease states like vascular diseases and angiopathic complications of diabetes. Therapeutic usage of TM in several pathological conditions including septic shock and vascular pathologies is under current investigation.