Increased wound collagen catabolism is among the defects of diabetic wound repair. We studied the interactions of topically applied insulin and epidermal growth factor (EGF) in diabetic rats. Polytetrafluoroethylene cylinders were implanted in 80 diabetic rats and removed on postoperative days 1, 5, 10, and 15. Cylinders were analyzed for collagen concentration and collagenase activity. The EGF and insulin promoted a 202% increase over controls in collagen synthesis by day 15, while diabetic rats that received EGF or insulin alone had significantly less collagen than controls. All groups that received insulin had lower collagenase activity than both controls and diabetic rats that received EGF. The individual effects of insulin and EGF added synergistically for a net gain in wound collagen content after 15 days. This gain was not observed with either EGF or insulin alone.