OBJECTIVE To investigate the effect of topical application of insulin on the burn wound healing in aging diabetes mellitus (DM) rats and to explore its mechanism. METHODS Seventy-five SPF Wistar rats (female and/or male), aged 12-24 months and weighing 300-350 g, were selected and randomly divided into group A (burn control group, n=25), group B (DM burn control group, n=25), and group C (DM insulin treatment group, n=25). The rats in group B and group C were fed with high-fat, high-protein, and high-sugar forage for 1 month and received intraperitoneal injection of streptozotocin (STZ) to establish experimental model of aging DM. The rats were fed with high-fat, high-protein, and high-sugar forage for another 8 weeks. Then, the deep second-degree burn model was established in the rats of group B and group C. The wounds in group A and B underwent local subcutaneous injection of 2 mL isotonic saline and group C received local subcutaneous injection of 0.1 U insulin. The rate of wound healing was calculated 7, 14, and 21 days after burn injury. At 1, 3, 7, 14, and 21 days after burn injury, HE staining observation, immunohistochemistry staining for CD34, detection of sugar and hydroxyproline (HOP) content in wound tissue, and microvessel density (MVD) calculation were performed. RESULTS At 7, 14, and 21 days after burn injury, the wound healing rates of group A and group C was significantly higher than that of group B (P < 0.05), and there was no significant difference between group A and group C (P > 0.05). Histology observation at 21 days after burn injury: in group A, certain degree of epithelization was evident in the wound epithelium; in group B, large quantity of necrotic tissue was evident; in group C, complete epithelization occurred in the wound epithelium with better epithelial cell differentiation and more neonatal collagen. For the sugar content in the wound tissue, group A was significantly lower than group B or group C at 1, 3, 7, 14, and 21 days (P < 0.05) and group C was significantly lower than group B at 7, 14, and 21 days (P < 0.05). For the HOP content in the wound tissue and the MVD count, group A or group C was significantly higher than group B (P < 0.05) and there was no significant difference between group A and group C (P > 0.05). CD34 expression: in group A, it was (+) at 7 days, (++) at 14 days, and (+++) at 21 days; in group B, it was (+) at 14 and 21 days; in group C, it was (++) at 7 days and (+++) at 14 and 21 days. CONCLUSIONS Topical application of insulin can promote the synthesis of wound collagen, accelerate the wound angiogenesis, and speed up the wound healing in aging DM rats.