The aim of this study to establish the effect of systemic N-acetylcysteine (NAC) administration on the oxidative–antioxidative balance, inflammatory markers, and collagen production during wound healing in diabetes. A total of 24 male Wistar albino rats were randomly divided into 4 groups: control, streptozotocin-induced diabetic model, NAC treatment group, and streptozotocin-induced diabetic model with NAC treatment. The dorsal circular wound model was created in model rats and systemic NAC application (IP, 60 mg/kg) was performed for 7 days in rats in the treatment groups. Lipid peroxidation, antioxidative parameters, NOx levels, and amount of collagen in wound tissue were determined by spectrophotometric methods. Inflammatory markers of wound tissue were detected by ELISA. In the wound tissues of untreated diabetic rats, lipid peroxidation and inflammatory markers were significantly increased. Superoxide dismutase and catalase activities, glutathione and NOx levels, and collagen production were significantly reduced. Following systemic NAC administration, antioxidant status and NOx levels were significantly improved and lipid peroxidation and inflammatory marker levels were remarkably reduced. Additionally, in the diabetic model-NAC treatment group, collagen production and wound contraction were significantly increased. Systemic NAC administration accelerates wound healing in diabetes by reducing oxidative stress and inflammation and increasing collagen production. As a consequence, systemic NAC therapy can be effective in ameliorating wound healing in diabetes.