Ischemia-reperfusion (IR) is a deleterious condition associated with liver transplantation or resection that involves pro-oxidant and pro-inflammatory mechanisms. Considering that Rosa Mosqueta (RM) oil composition is rich in protective components such as α-linolenic acid (ALA) and tocopherols, we studied the effects of RM oil supplementation given prior to an IR protocol. Male Sprague-Dawley rats receiving RM oil (0.4 mL d-1) for 21 days were subjected to 1 h of ischemia followed by 20 h reperfusion. Parameters of liver injury (serum transaminases, histology), oxidative stress [liver contents of protein carbonyls, thiobarbituric acid reactants, Nrf2 activity and its target mRNA expression of heme oxygenase-1 (HO-1) and NADPH-quinone oxidoreductase-1 (NQO-1)] and inflammation [nuclear factor-κB (NF-κB) and its target mRNA expression of tumor necrosis factor-α (TNF-α) and interleukine-1β (IL-1β)] were studied. RM oil increased liver ALA and its derived EPA and DHA fatty acids' contents, with enhancement in those of α- and γ-tocopherols. IR induced inflammatory liver injury, with enhancement in serum transaminases, oxidative stress-related parameters with reduced Nrf2 signaling, and higher pro-inflammatory cytokines, indexes that were attenuated or abrogated by RM oil pretreatment. It is concluded that RM oil supplementation represents a novel non-invasive preconditioning strategy against liver injury induced by IR that has potential clinical applications in metabolic stress conditions.