The high capacity of liver regeneration after partial hepatectomy (PH) is well known. This study investigated the role of the antioxidant defense system in regeneration among Wistar-albino male rats subjected to 70% partial hepatectomy after a pretreatment period of 2 weeks with eicosapentanoic acid (EPA) rich fish oil (FO), first pressed virgin olive oil (OO), or vitamin E. The control group of 10 rats underwent PH only. On postoperative day 3, all rats were humanely killed. Liver sections of animals treated with FO or vitamin E showed significant increases in regeneration within both liver parenchyma and cut surface compared with the control group (P < .05). Liver sections of OO displayed an insignificant increase in liver regeneration (P > .05), with less increase in parenchyma than of the cut surface. The enhancement of the liver parenchymal regeneration in the FO group was significantly greater than that of the vitamin E group. Concerning liver function tests (LFT), there was no significant difference among the groups. When the treatment groups were compared to the control group glutathione (GSH) levels were increased and content of malondialdehyde (MDA), nitric oxide (NO), and superoxide dismutase (SOD) were decreased. Based on these results, we concluded that after 70% PH in rats, the liver parenchyma and cut surface regeneration were greatest with FO and least with OO treatment. Both FO and vitamin E served to improve the antioxidant defense system more than OO treatment.