Objectives: Tissue factor (TF) is the main initiator of the extrinsic coagulation pathway through factor VII (FVII) activation, which is physiologically inhibited by tissue factor pathway inhibitor (TFPI). Alteration of this pathway has been described in Type 2 diabetes mellitus (T2DM). The aim of this study is to assess TF and TFPI plasma levels and FVII coagulant activity (FVIIa) in T2DM in relation to cardiothrombotic disease and their correlation to metabolic and clinical behavior of the patients.Methods: The study was conducted on 80 T2DM patients divided to accordingly; groupI: 40 patients without a history or clinically detected heart disease, and groupII: 40 patients with a history of myocardial infarction compared to 30 controls. The patients were recruited from Ain Shams University diabetes clinic from September 2007 to February 2009 after informed consent was obtained. Peripheral blood samples were taken for measurement of plasma TF and TFPI levels using ELISA technique and quantitative FVIIa using FVII deficient plasma.Results: Plasma levels of TF, TFPI and FVIIa were significantly higher in T2DM patients compared to the controls (p<0.001). TF (236.50±79.23)and TFPI (242.33±85.84)were significantly higher in group II, compared to group I (150.33±81.16), (152.8± 82.46), (p<0.001). TF and TFPI were significantly correlated to body mass index and glycemic control. Also, TF and TFPI were significantly higher in hypertensives (p=0.001) and dyslipidemics (p=0.006) but not in smokers (p=0.64), (p=0.11) respectively.Conclusion: There was a correlation between high TF, TFPI plasma levels, FVIIa activity and cardiothrombotic complications in T2DM especially in the presence of high risk factors such as poor glycemic control, dyslipidemia and obesity. Future target therapy against TF may be beneficial for T2DM patients.