Summary Background & aims The aim of this study was to investigate the effect of a fermented substance from Saccharomyces cerevisiae (FSSC) on the liver fibrosis induced by chronic carbon tetrachloride (CCl 4) administration in rats. Methods Rats were divided randomly into four groups: control, CCl 4, and two FSSC groups. Except for rats in the control group, all rats were orally administered CCl 4 twice a week for 8 weeks. Rats in the FSSC groups were treated daily with FSSC (0.5 or 1.5 g/kg) through gastrogavage for the entire experimental period. Results CCl 4 caused liver damage, as characterized by increases in levels of plasma transaminase, hepatic malondialdehyde, and hydroxyproline, in addition to increases in spleen and liver weights and decreases in plasma albumin levels. Compared with CCl 4 group, FSSC (1.5 g/kg) treatment significantly decreased the spleen ( P < 0.01) and liver ( P < 0.01) weights, the activities of transaminase ( P < 0.05), and levels of hepatic malondialdehyde ( P < 0.05) and hydroxyproline ( P < 0.01); however, the treatment increased plasma albumin level ( P < 0.05). The pathological results also showed that FSSC (1.5 g/kg) suppressed hepatic inflammation, steatosis and necrosis. Data for hepatic fibrosis were expressed as the mean percentage of the total hepatic area in the tissue sections. FSSC (1.5 g/kg) treatment significantly decreased the hepatic fibrosis (12.8 ± 1.2 and 6.4 ± 0.7 in CCl 4 and FSSC group, respectively, P < 0.001). RT-PCR analysis showed that FSSC (1.5 g/kg) treatment decreased the expression of methionine adenosyltransferase 2A ( P < 0.01), collagen (α1)(I) (3.15 ± 0.05 and 1.52 ± 0.04 in CCl 4 and FSSC groups, respectively, P < 0.001), and transforming growth factor-β1 (2.50 ± 0.05 and 1.21 ± 0.04 in CCl 4 and FSSC groups, respectively, P < 0.001), apart from increasing the expression of methionine adenosyltransferase 1A ( P < 0.05). Conclusion These results showed that FSSC protects the liver against CCl 4 damage in rats.