A procoagulant state has been found to exist in diabetes mellitus. There may be activation of the intrinsic coagulation system, decreased fibrinolytic activity, or alterations in platelet function. Intensive glycemic control with insulin is effective in reducing the impact of this procoagulant state by favorably affecting all three components of the system. Decreased fibrinolytic activity, as influenced by plasma PAI-1 levels, may be favorably affected by weight loss, exercise, a low-GI diet, or by metformin, thiazolidinediones, gemfibrozil, and ACE inhibitor therapy. Insulin has variable effects on plasma PAI-1 activity. Estrogens will lower the elevated PAI-1 levels seen in the menopausal state. Collaborative trial evidence supports the use of low-dose aspirin as a primary or secondary prevention strategy in diabetic persons who are at high cardiovascular risk. A recent study suggests that this category includes virtually every type 2 diabetic individual in the United States. The American Diabetes Association recommends enteric-coated aspirin, 81 to 325 mg/day, as the first choice. In the case of aspirin allergy, clopidrogel is an alternate choice. Thus, recognition of and therapy for a procoagulant state in diabetes mellitus is likely to result in a decrease in the atherothrombotic events that characterize the later stages of this disease.