Background: Melatonin (Mel) has a very potent antioxidant activity, depending mainly on its capacity to act as an electron donor. Recently, the antioxidant property of Mel has been much emphasized. In this study, the dorsal skin flap model was used to investigate the effect of Mel in flap viability in rats. Material and Methods: Totally 28 Wistar Albino rats were divided into four groups: control group (C) (n = 7), local treatment group (L) (n = 7), systemic low-dose melatonin treatment group (LT) (n = 7), and systemic high-dose melatonin treatment group (HT) (n = 7). The necrosis rate of the skin flaps was observed seven days after the operation by a blinded observer. Oxidative stress was assessed by determining malondialdehyde (MDA) level, and effects of melatonin on antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) were measured. Vascularity, epithelial thickness, and fibroblast proliferation of dorsal skin flaps were assessed histologically. Results: Amount of MDA were found significantly lower (p < .05), and the flap viability, CAT, SOD, vascularity, fibroblast proliferation, and epithelial thickness were found significantly higher (p < .05) in groups HT than in groups C, L, and LT statistically. Conclusion: Our results showed that the usage on different doses of melatonin could play an important role in the process of flap viability and further studies will focus on these areas of interest.