Background: Tissue factor (TF) is the key initiator of the coagulation cascade. Recent evidence suggests that TF plays a role in renal fibrin formation and renal failure in experimental kidney disease. We hypothesized that hyperglycemia is an important stimulus of TF expression in the kidney. Methods: Mice were injected with streptozotocin (STZ) (200 mg/kg) or with control buffer. Three or 10 weeks after injection, fibrin, thrombin and TF staining and TF activity were evaluated in the kidney. The effect of hyperglycemia on TF expression and secretion by tubular epithelial cells was measured in vitro. Results: Kidneys of STZ-treated mice showed a marked increase in thrombin staining (3.0 ± 0.5 vs. 1.2 ± 0.11) (p = 0.002) and an increase in TF clotting activity 10 weeks after STZ injection (33.9 ± 1.3 vs. 25.4 ± 1.0 s) (p < 0.0001). Increased glomerular fibrin deposition was present in 3 out of 6 diabetic mice. Tubular cells incubated with D-glucose (25 mmol/l) for 48 h displayed increased cellular TF (p = 0.05). However, soluble TF levels and TF activity in supernatant of cells incubated with D- or L-glucose were not different. Conclusions: These data suggest that hyperglycemia is a causal factor in procoagulant activity associated with diabetic nephropathy.