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<p>Abstract</p> <p>Background</p> <p><it>Cichorium glandulosum</it> Boiss. et Huet is used for treatment of liver disorders, and its effects are attributed to sesquiterpenes. This study aims to investigate the hepatoprotective effects of a sesquiterpene-rich fraction (SRF) from the aerial part of <it>C. glandulosum</it> on carbon tetrachloride (CCl₄)-induced acute hepatotoxicity in mice, and on priming with Bacillus Calmette–Guerin (BCG) followed by lipopolysaccharide (LPS)-induced immunological liver injury in mice.</p> <p>Methods</p> <p>SRF was suspended in water and administered to mice at 0.05, 0.10 and 0.20 g/kg body weight for 7 consecutive days. An active control drug (bifendate pills) was suspended in distilled water and administered to mice at 0.40 g/kg body weight for 7 consecutive days. Hepatotoxicity was induced by intraperitoneal injection of 0.1% CCl₄ (0.2 mL/mouse) at 13 h before the last drug administration, or by tail intravenous injection of BCG (0.2 mL/mouse) before the first drug administration and LPS (0.2 mL/mouse; 8 μg) at 15 h before the last drug administration. Blood samples and the livers were collected for evaluation of the biochemical parameters of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin (TBIL).</p> <p>Results</p> <p>SRF significantly reduced the impact of CCl₄ toxicity. The highest dose of SRF (0.20 g/kg) was the most effective, reflected by significant reductions in the levels of AST (<it>P</it> = 0.001), ALT (<it>P</it> = 0.000) and TBIL (<it>P</it> = 0.009). The serum enzymatic levels induced by BCG and subsequent LPS injection were significantly and dose-dependently restored by SRF, reflected by significant reductions in the levels of AST (<it>P</it> = 0.003), ALT (<it>P</it> = 0.003) and TBIL (<it>P</it> = 0.007) for the highest dose of SRF (0.20 g/kg).</p> <p>Conclusion</p> <p>SRF is hepatoprotective in animal models of chemical and immunological acute liver injury.</p>