The purpose of this study was to investigate the protective effect of polysaccharides from Boschniakia rossica against hepatotoxicity induced by carbon tetrachloride (CCl₄). Boschniakia rossica polysaccharides was administered intragastrically once daily for 7 days. One hour after the final treatment, mice were treated intraperitoneally with 80 mg/kg of CCl₄. CCl₄-induced hepatotoxicity was manifested by increased levels of serum marker enzymes and hepatic lipid peroxidation, and by decreased potential of hepatic antioxidative defense system. CCl₄ challenge also resulted in elevated serum tumor necrosis factor-α and hepatic nitric oxide level, and up-regulation of inducible nitric oxide synthase and cyclooxygenase-2 proteins of liver tissue. Pretreatment of mice with Boschniakia rossica polysaccharides reversed these altered parameters of mice with liver injury induced by CCl₄. Furthermore, caspase-3 cleavage and activities, and DNA fragmentation of liver in mice treated with Boschniakia rossica polysaccharides were decreased than mice treated with CCl₄ alone. Hepatoprotective effect of Boschniakia rossica polysaccharides was further demonstrated by histopathological examination of liver sections. The results indicate that Boschniakia rossica polysaccharides play a protective role in CCl₄-induced acute liver injury and the hepatoprotective effect of Boschniakia rossica polysaccharides may be due to elevated antioxidative defense potentials, suppressed inflammatory responses and apoptosis of liver tissue.