Wound healing is a complex process affected by various conditions, including oxidative stress. The present study explored the time-dependent effects of platelet-derived growth factor (PGDF) and vascular endothelial growth factor (VEGF) administration on oxidative markers during acute stage wound healing. Thirty-six Wistar rats were distributed into three major groups; skin wounds were inflicted in all groups. The wounds were either left untreated (control group), treated topically with blank chitosan gel (blank chitosan gel group), or treated topically with a combination of PDGF and VEGF in chitosan gel (PDGF + VEGF chitosan gel group). Wounds were sampled on postsurgery days 3 and 7; samples were assayed for the oxidant markers nitric oxide (NOx) and thiobarbituric acid-reactive substances (TBARs) and the antioxidant markers glutathione (GSH), ascorbic acid (AA), and superoxide dismutase (SOD) activity. PDGF + VEGF administration increased and decreased NOx levels on days 3 and 7, respectively. PDGF + VEGF administration lowered TBARs levels, compared with blank chitosan gel administration, on day 7. PDGF + VEGF administration increased GSH levels. These results demonstrate that PDGF + VEGF administration changes oxidative status of wound tissue. This study provides valuable insights for the development of therapeutic targets that promote wound healing.