Extracellular glycosylation of proteins in diabetics may contribute to observed impairments in wound healing. We investigated the interactions of blood glucose concentration and wound collagen glycosylation, collagen content, and proteolytic activity during wound healing in diabetic animals. Rats were made differentially hyperglycemic with intraperitoneal injection of streptozotocin (0-65 mg/kg body weight). Animals with blood glucose concentrations greater than 240 mg glucose/dL were classified as diabetic, those with blood glucose concentrations less than 160 were grouped as nondiabetic. Polytetrafluoroethelene (PTFE) wound cylinders were surgically implanted in 32 rats and removed on postoperative day 5. Harvested cylinders were analyzed for hydroxyproline content, collagen glycosylation, and collagenase and protease activity. Collagenase activity was 14% higher in diabetics than nondiabetics (P less than .001). Glycosylation of wound collagen averaged 48.0% higher in diabetics (P less than .001). Wound hydroxyproline content was 39% lower in diabetics (P less than .05). Studies show a high degree of correlation (Pearson) of wound collagen nonenzymatic extracellular glycosylation (NEG) with mean blood glucose concentration (r = .98, P less than .001). Wound collagen glycosylation correlates strongly with both protease activity (r = .86, P less than .001) and collagenase activity (r = .83, P less than .001). This study demonstrates a significant blood glucose concentration dependent increase of glycosylation in newly synthesized collagen in hyperglycemic animals that is associated with increased collagenase activity and decreased wound collagen content.