Introduction: Muscle-flap transferring is a routine approach utilized in reconstructive operations; however, flap morbidity is often a source of post-operative difficulty. Ischemia-Reperfusion Injury (IRI) is an important contributor to the viability of flaps after transferring. The goal of this research was for assess the probable useful impacts of ozone on flap survival in a rat muscle-flap design. Materials and Methods: We examined the effects of postconditioning ozone administration on viability of pedicled composite flaps. Twenty-eight Wistar rats were randomized into four groups: sham-operated (S), ischemia-reperfusion (IR), sham-operated + ozone (O), IR + ozone (IR + O), respectively. The animals were sacrificed on the eighth day. In a general histological evaluation, flap tissues were examined with a light microscope, and apoptotic cells were counted. The Apoptotic Index (AI) was then calculated. Flap-tissue samples were sent for analyses of malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and protein carbonyl (PCO), and blood samples were sent for analyses of Total Oxidant Score (TOS), and Total Antioxidant Capacity (TAC). Data were evaluated statistically using the Kruskal–Wallis test. Results: The histomorphometric score was remarkably greater in O (p =.002). The AI was greater in IR (p =.002). The antioxidant parameters values as regards SOD, GSH-Px, CAT, and TAC were found to be greater in O (p <.005). The oxidant parameters values as regards MDA, PCO, TOS were found to be greater in IR (p <.005). Discussion: The current research indicates that ozone application can attenuate the muscle-flap injury brought about by IR through triggering the increase of the antioxidant capacity.