Metabolic syndrome (Mets) is the medical term for a cluster of metabolic abnormalities that increases in individuals risk of T2DM and CVD. The component of MS are glucose intolerance, obesity, hypertension and dyslipidemia. An insulin resistance is the key phase of metabolic syndrome constitutes the major risk factor for the development of diabetes mellitus. Objectives: The present study aimed to comprise Copeptin, E-Selectin and Thrombomodulin in addition to insulin resistance values among two study groups, metabolic syndrome patients and diabetes mellitus type2 patients . Subjects: The present study included 50 metabolic syndrome patients, 50 cases who suffered T2DM as pathological control, finally 50 individuals as healthy control. Methods: current study investigated the association between Copeptin, E-Selectin, and Thrombomodoluin with development risk effect of endothelial dysfunction in MS and T2DM patients by applying ELISA kit method. Results: current work showed a highly significant variations among study groups, no significant differences were shown when the comparison was carried out between two genders of the same subgroups.