PURPOSE: Lipid peroxidation and consequent reactive oxygen species in the setting of oxidative stress have crucial roles in liver regeneration, which may adversely affect the regeneration itself and lead to liver failure. The aim of the current study is to investigate whether omega-3 fatty acid supplementation inhibits oxidative stress in an experimental model of liver regeneration. METHODS: Forty rats were allocated to four groups. Rats in group A received a sham operation. Rats in group B were subjected to right portal vein ligation (RPVL) and saline infusion. Rats in groups C and D were subjected to RPVL and total parenteral nutrition (TPN) with an all-in-one admixture containing a soybean oil based lipid emulsion. Rats in group D were additionally supplemented with omega-3 fatty acid infusion. Oxidative stresses in the blood and liver were measured by glutathione, superoxide dismutase, catalase, glutathione peroxidase, malondialdehyde, and nitric oxide. RESULTS: Omega-3 supplementation to the TPN solution significantly corrected alterations in the blood and tissue concentrations of oxidants and anti-oxidants during regeneration (P < 0.05). CONCLUSION: Omega-3 fatty acid supplementation to the TPN solution revealed promising results in removal of oxidative stress that emerges during liver regeneration.