Background Obesity has emerged as the biggest pandemic of our times growing parallel to type 2 diabetes. Its managment by several therapeutic approaches has been unable to completely inhibit different pathways involved the reactive oxygen species (ROS) production, lipid peroxidation and PKC activation. Coupled with recent evidences that highlight the role of ROS in the onset and progression of type 2 diabetes, the antioxidants have taken prime focus as potential pharmacological approach. Krill oil enriched in marine ω3 regulates numerous anti-inflammatory and antioxidative processes. The aim of our study was to determine whether enrichment with Krill oil (KO) protects insulin resistant target tissues of high fat-diet-fed rats against oxidative stress features. Methods The 6 – to 8-week-old mal Wistar rats weighing 160-200 g were randomly divided into three experimental groups consisting of 10 each and received one of the following three experimental diets during 8 weeks : standard laboratory chow (18kcal% fat, 58kcal% carbohydrates, 24kcal% proteins) or one of the two high energy diets : high fat diet (HFD : 60kcal% fat, 20kcal% carbohydrates, 20kcal% proteins). The second diet (HFD-KO) differs from the HFD by the substitution of part of fat (18 kcal%) by the Krill oil. At sacrifice, reliable markers for oxidative stress, 7,8 dihydro 8oxo 2deoxygua-nosine (8 OH Gua), 8iso PGF2alpha, malondialdehyde (MDA) and protein carbonyl levels were measured in liver, abdominal adipose tissue (AAT) and in the muscle. In addition, antioxidant capacity was determined by calculating total glutathione level and catalase and SOD activity in the latter tissues. Results The HF diet induced oxidative stress characterized by elevated MDA, carbonyls and 8 isoPGF2alpha contents and DNA damage as indicated by a higher 8OH Gua levels with a decrease of antioxidant defense (SOD, CAT, Glutathione). The KO treated-rats liver and AAT medium displayed a significant decrease in 8 – iso PGF2alpha, MDA and protein carbonyl levels and an increased SOD, CAT activity and total glutathione content compared to HFD. However the latter group muscle revealed a higher total glutathione levels and a slight decrease in MDA and 8 iso-PG2alpha levels while the catalase activity increased after the enrichment with the KO. The 8OHGua levels were significantly lower in the liver and AAT KO supplemented group as compared to HFD but this parameter was not affected in muscle. Conclusions Krill oil may be a therapeutic useful compound by preserving antioxidant mechanisms and protecting cellular components of insulin resistant-related-several peroxidative damages.