We studied the toxicity dose and toxicity mechanism of rhubarb, a Chinese traditional medicine, by administering different doses to rats and examining the effects on the liver. Kunming rats were given intragastric administration of large, medium, small and minimum doses of rhubarb twice daily for five consecutive days. Then the general status of the rats, the hepatoenzymological data, histopathology of liver, and TNFα mRNA expression were examined. The following results were obtained. 1. The general status of rats deteriorated with the increase in rhubarb dosage. The physical status of rats in the control group and minimum dose group were normal, but the status in other groups gradually deteriorated along with the increase in rhubarb dose. 2. Regarding the changes of hepatoenzymology profile, alanine aminotransferase and gamma-glutamyltransferase were elevated with increase in rhubarb dose; while the difference between normal control group and minimum dose group was unremarkable, the differences among other groups were obvious. 3. Examination of H&E-stained slides showed fatty degeneration of the liver starting from the minimum dosage group. This phenomenon is aggravated with increase in rhubarb dosage. 4. TNFα expression was elevated significantly with increase in rhubarb dosage, beginning from the minimum dosage group. The present results showed that even a small dose of rhubarb given to rats by the intragastric route for five consecutive days was toxic to the liver, and the toxic effect was enhanced with increase in rhubarb dosage. The toxic effect of excessive intake of rhubarb to the liver is mainly manifested as fatty degeneration. TNFα, an injury factor leading to fatty degeneration of cells, was probably involved in the hepatotoxicity by excessive intake of rhubarb.