Impaired wound healing is characteristic of diabetic patients. Potential reasons include poor inflammatory response, granulation tissue formation, and abnormal patterns of cytokine release and response. Vascular endothelial growth factor, abnormally regulated during healing in diabetics, is the major factor stimulating angiogenesis during normal wound healing. We tested our hypothesis that topically applied vascular endothelial growth factor would improve wound closure rates in diabetic animals in a full-thickness wound model in genetically diabetic mice (C57 BL/KsJ db/db). Animals received either 1.0 micro g of vascular endothelial growth factor165 or polyethylene glycol alone topically to wounds daily between days 0 and 4 post-wounding. Wound area was measured at days 0, 5, 10, 15, and 21. Data were analyzed using probit analysis and expressed as length-of-time (LT) to 50, 90, and 95% wound closure. Among untreated animals, nondiabetics had an LT50 of 8.5 days (fiducial limits 8.3-8.7), while diabetics had an LT50 of 15.8 days (15.6-16.1). Vascular endothelial growth factor-treated animals had LT50 values of 7.8 (7.6-8.1) and 11.8 days (11.6-12.0) for nondiabetics and diabetics, respectively, representing a 25% improvement in time to 50% closure in treated diabetics. We conclude that topically applied vascular endothelial growth factor improves time to wound closure in the genetically diabetic mouse model.