The administration of a low-carbohydrate, and high-fat ketogenic diet (KD) has been demonstrated to exert beneficial effects on gastrointestinal mucosa in rats. Therefore, the present study was aimed to investigate whether the KD treatment, able to reduce the inflammation at the intestinal level, could also affect rat liver function. After weaning at 5 weeks of age, 12 Wistar rats were fed standard diet (control group), and 13 animals were fed KD. After ten weeks of treatment, animals were sacrificed and the liver from each animal was collected and stored at -80°C until assayed. Fatty acids extracted from liver tissue were quantified by a gas chromatographic method. Western blotting analysis and ELISA method were used to evaluate the inflammation and antioxidant biomarkers in rat liver, respectively. The levels of single saturated fatty acids and monounsaturated fatty acids were significantly decreased in hepatic tissue after KD treatment. A significant decrease was also observed for the content of arachidonic acid, an omega-6 polyunsaturated fatty acid. All main omega-3 polyunsaturated fatty acids, except for eicosapentaenoic acid, were significantly increased in liver tissue from rat treated with KD. Compared to the control group, a significant increase of the SOD 1 and SOD 2 protein enzymes, was found in the liver of KD-treated rats. KD treatment on the one hand promotes the increase of tissue inflammation status in the rat liver, on the other it was able to activate defense mechanisms to protect liver environment.