Background: Carbon tetrachloride (CCl4) is one of the most widely used Hepatotoxin that is known to induce oxidative stress and causes hepatic damage by the formation of reactive free radicals in laboratory animals. Objective: This study aims to investigate the hepatoprotective role of pomegranate seed oil (PSO) on histological structure, some biochemical parameters and lipid peroxidation on CCl4-induced acute and chronic liver injury induced rats. Materials and Methods: The study material comprised 80 male Wistar albino rats. They were divided into two study groups including 40 rats for acute and 40 rats for chronic hepatotoxicity induction by CCl4. Hematoxylin and eosin staining was used to evaluate degree of steatosis, inflammation, necrosis, and fibrosis semiquantitatively. Blood serum aspartate transaminase, alanine transaminase, and alkaline phosphatase enzyme activities and glucose, triglyceride, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, total protein, albumin and liver malondialdehyde, and nitric oxide levels were measured. Results: All control and only PSO given animals liver showed normal histological architecture, but in the acute CCl4-treated animals, an intensive macro and microvesicular steatosis, mononuclear inflammatory cell infiltrations in portal area and parenchyma, and necrotic alterations; in the chronic CCl4-treated group, additionally to acute findings mild-to-severe fibrosis with lobulation formation were observed. Conclusion: The results suggest that administration of PSO has partially ameliorative effects on biochemical and lipid peroxidation parameters in acute period, but it has no effect on the recovery of liver tissue damage or histopathological changes and biochemical parameters induced by CCl4 in chronic period.