We characterized a factor important for the normal procoagulant activity in human urine and measured urinary tissue factor (TF) and thrombomodulin (TM) levels in patients with diabetes mellitus (DM). Urine shortened normal plasma-based clotting time, which is inhibited by antibody to the human TF. TF in urine presents in membrane-nonassociated and associated forms. The urine TF antigen levels in DM patients were significantly lower than those in healthy subjects, particularly in DM patients without retinopathy. Levels of TM in patients with DM and normal subjects were similar. Although urinary TF might be necessary to repair tissue injury of damaged sites in the excretory pathway of urine, the clinical relevance of the reduced TF in the urine needs further investigation.