Purpose: In this study the effects of leptin administration on wound healing and nitric oxide levels in healthy and diabetic rats (with streptozotocin, STZ) are investigated. Material and methods: Twenty four male Wistar Albino rats were used in this study. The animals were divided into two groups as non-diabetic (NDM) (n=12) and diabetic (STZ-DM) (n=12). Seven days after the STZ administration (55mg/kg, intraperitoneal (i.p.), single dose), rats with blood glucose level of 300 mg/dl and over were considered diabetic. Under general anesthesia, all rats were subjected to excisional wound formation on the back and on both sides of the central line (3 on the each side) wim 6-mm diameter dermal punch. The rats were divided into leptin and vehicle (PBS) subgroups. In leptin group, recombinant rat leptin and/or PBS was administered intraperitoneally (0.1 mg/kg/day) and topically (5 μg/wound/day) to the animals for 5 days after the wound formation. After administrations, the rats were sacrificed via cardiac puncture under anesthesia and wound tissue samples were taken. The wound samples were examined under light microscopy. The nitrite-nitrate levels which are the indicator of nitric oxide levels in wound tissue were measured and expressed as NOx. Results: In histological evaluation, it was observed that, the inflammation continued and collagen production and epithelialization were incomplete in diabetic rats. In topical leptin administrated NDM rats and systemic+topical leptin administrated STZ-DM rats, epithelialization and collagen organization was significantly improved in the wounds compared to vehicle subgroup with no leptin treatment. When wound NOx levels in leptin group are compared to vehicle subgroup with no leptin treatment, NOx levels were found to be significantly lower. Conclusion: Our findings point out that leptin has a positive effect on wound healing when it is administered only topically in healthy rats. However, it has a positive effect on wound healing when it is administered systemically and topically together in rats with diabetes. The NOx levels in wound tissue appear to be related to the degree of wound inflammation and hyperglycemia.