Objective. This study evaluates the effects of topical and systemic N-acetyl cysteine (NAC) treatment on wound healing in a diabetic rat model. Materials and Methods. A total of 48 male Wistar Albino rats were randomly divided into 4 groups of 12. Diabetes was induced with an intraperitoneal injection of 60 mg/kg streptozotocin. A 2-cm x 1-cm full-thickness wound was created on the back of each animal. In group 1 (control) and group 3 (systemic NAC), the wounds were closed with 0.9% sodium chloride-treated sterile gauze. In group 2 (topical NAC) and group 4 (topical + systemic NAC), the wounds were closed with sterile gauze treated with 3 mL (300 mg) of NAC. The animals in groups 3 and 4 were administered 200 mg/kg of NAC once daily through an orogastric tube. On days 1 and 14, the wounded areas were measured. Tissue and blood samples were taken on day 14 for histopathological and biochemical examination. Results. On day 14, the wounded area in groups 2, 3, and 4 was found to be smaller than in group 1 (control). Histopathologically, epithelialization and fibrosis scores were significantly lower, whereas the inflammation score was higher in group 1 than in the other groups. Tissue oxidative stress parameters (malondialdehyde, fluorescent oxidation products, total oxidative stress) were higher in the control group than in the other groups. In groups 3 and 4 (which received systemic NAC), the oxidative stress parameters in serum samples were lower than those of the control group and group 2. Serum sulphydryl levels were the lowest in group 1. Conclusions. The results of this study show that both topical and systemic administration of NAC improved wound healing in a diabetic rat model. This effect of NAC may be related to its antioxidant properties since a reduction in oxidative stress parameters in both tissue and serum were shown in the present study.