Abstract: Tumor necrosis factor (TNF) has been well characterized as a prominent mediator in the development of liver injury. Effects of silymarin(SB) on mouse liver damage, TNF production and activity were studied. Pretreatment with SB(25～50 mg·5kg^-1, ip, bid×3 d) before the lipopolysaccharides (LPS) injection markedly alleviated liver injury and diminished LPS-induced TNF production in Propionibacterium acnes (PA) primed mice. SB(12.5～50 μg·5mL^-1 ) significantly inhibited LPS-induced TNF release from mouse peritoneal macrophage in a concentration dependent manner. SB(12.5～100 μg·ml^-1 ) was also shown to markedly reduce TNF cytotoxicity on human hepatic cell line GSG-7701 and mouse fibroblastic cell line L929 cells concentration dependently. These results suggest that inhibition of TNF production and its actions may be involved in the mechanism of protective action of SB on liver damage.