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Chronic liver diseases are clinically silent and responsible for significant morbidity and mortality worldwide. β-Sitosterol (BSS), major phytosterol in plants, has a wide spectrum of protective effect against various chronic ailments. We investigated the hepatoprotective effect of BSS against carbon tetrachloride (CCl 4 )-induced chronic liver injury in rats. Thirty rats were divided into five groups, with six animals in each group. Group I rats served as control while groups II, III, IV, and V rats were injected intraperitoneally with CCl 4 (0.2 mL/100 g b.w. in olive oil (1:1)) for 7 consecutive weeks. After 7 weeks, group II rats were left without any treatments and served as CCl 4 alone group, while groups III, IV, and V rats were treated with BSS 25 and 50 mg/kg b.w. and silymarin 100 mg/kg b.w. as oral post-treatments respectively, for the next 4 weeks. At the end of the experiment, hepatotoxicity marker enzymes in serum, oxidative stress, and fibrosis marker were analyzed. CCl 4 administration caused significant elevation of marker enzymes of hepatotoxicity in serum and increased lipid peroxidation and fibrosis markers such as hydroxyproline, collagen, α-smooth muscle actin, vimentin, desmin, and matrix metalloproteinases 9 in liver tissue of rats. This treatment also caused a significant diminution of intracellular enyzmic antioxidants such as SOD and CAT in the liver tissue of rats. All the above adversities were significantly mitigated by the BSS post-treatments. The results suggest that BSS could have a hepatoprotective effect against oxidative stress-mediated CLD induced by CCl 4 .