Following a persistent liver damage, a pathological process known as hepatic fibrosis arises due to an imbalance in the liver's repair system. Liver fibrosis was primarily caused by chemicals, metabolic intermediates, and biological agents such as viruses. Aim: This study aims to investigate the biochemical and histopathological changes in the liver induced by Carbon Tetrachloride (CCl4) toxicity, and mitigating the potential effect losartan potassium (LP) and losartan potassium nanoparticles (LP-NPs) on experimentally induced CCl4 liver fibrosis. Methods: A total of 32 adult male Sprague Dawley albino rats weighing (180-200) gm were included in this study. The rats were randomized into four groups (control group, model group, losartan potassium, and losartan potassium nanoparticles treated groups), in which all rats were given the intra-peritoneal injection of CCl4 (2 ml/kg dissolved in a 1:1 ratio of olive oil, twice weekly for 6 weeks) except for rats of control group. Rats of losartan potassium, and losartan potassium nanoparticles treated groups were treated with LP and LP-NPs (orally in a dose of 10mg/kg/day along with ccl4 injection). After 10 weeks liver tissue and serum samples of all rats were examined. The structural and biochemical changes of the liver were measured. Results: results showed that CCl4 toxicity induced abnormal liver function, severe liver architecture deformity with pseudoloboule formation and cellular inflammation with infiltration reported in most of the portal areas, fibrous septa and the liver lobules. In addition, collagen I and II were significantly expressed in model group compared to control rats. However, at both losartan potassium, and losartan potassium nanoparticles treated groups, these changes were reversed with strong advantage to LP-NPs. The administration of LP and LP-NPs significantly improved the liver function values, hepatic architecture and suppressing the overproduction of collagen fibrils Conclusion: The present study highlights that LP or delivered LP-NPs nanoparticles could have a protective effect on liver functions and architecture in the rat liver of CCl4 induced liver injury