AIM: To investigate the possible mechanism of the protective effects of a bioactive fraction, Ganoderma lucidum proteoglycan (GLPG) isolated from Ganoderma lucidum mycelia, against carbon tetrachloride-induced liver injury.METHODS: A liver injury model was induced by carbon tetrachloride. Cytotoxicity was measured by MTT assay.The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined with an automatic multifunction-biochemical analyzer and the levels of superoxide dismutase (SOD) and TNF-α were determined following the instructions of SOD kit and TNF radioimmunoassay kit. Liver sections were stained with hematoxylin and eosin (H&E) for histological evaluation and examined under light microscope.RESULTS: We found that GLPG can alleviate the L-02liver cells injury induced by carbon tetrachloride (CCl4)through the measurements of ALT and AST activities and the administration of GLPG to L-02 cells did not display any toxicity. Furthermore, histological analysis of mice liver injury induced by CCl4 with or without GLPG pretreatment indicated that GLPG can significantly suppress the toxicity induced by CCl4 in mice liver. We also found that GLPG reduced TNF-α level induced by CCl4 in the plasma of mice, whereas increased SOD activity in the rat serum.CONCLUSION: GLPG has hepatic protective activity against CCl4-induced injury both in vitro and in vivo. The possible anti-hepatotoxic mechanisms may be related to the suppression of TNF-α level and the free radical scavenging activity.