To observe the degree of hepatotoxicity damage to rats and the correlation with oxidative damage mechanism after taking a large dose of crude extracts of total saikosaponins for a long time. According to 45-day toxicity experimental methods, rats were successively administrated with crude extracts of total saikosaponins. High, middle and low dose were respectively 100, 50, 10 mg x kg(-1) calculated by total saikosaponins. The general conditions were observed and the related index of liver function, the metabolism condition of lipids, the glycometabolism, the level of TBIL were determined and the histopathologic examination of hepatic tissue were examined. The content of total-SH in serum, the level of MDA, the activity of SOD and the content and activity of GSH and GSH-Px in serum and liver tissue were detected. The crude extracts of total saikosaponins can increase the activity of ALT and AST in blood, increase liver weight and the ratio of liver to body, increase the content of TG in blood and liver. The effect on CHO in blood and Gn in liver is not obvious. Only high dose group's effect on TBIL can be observed. The hepatic cell damage is obvious in the histopathologic examination of hepatic tissue. The crude extracts of total saikosaponins can increase the content of total SH in blood, the content of MDA and GSH in blood and liver, while decrease the activity of SOD and GSH-Px in blood and liver. The above-mentioned changes gradually aggravates with dose increasing, and is obvious compared with distilled water control group. The crude extracts of total saikosaponinscan induce hepatotoxicity damage, and the mechanism of hepatic damage is related with oxidative damage mechanism.