To explore the changes of the chemical components in Radix et Rhizoma Rhei after processing and the hepatotoxicity-alleviating mechanism.Methods:Ultraviolet spectrophotometry and high-performance liquid chromatography(HPLC) were used to analyze the changes of tannins，total anthraquinones，and free anthraquinones during the processing of Radix et Rhizoma Rhei.In addition，acute toxicity experiment was carried out on zebrafish to evaluate the hepatotoxicity of the medicinal before and after processing.Results:The content of tannins，total anthraquinones，and free anthraquinones in the raw medicinal material was 3.59%，1.96%，and 1.03%，respectively.After processing，the content of tannins，total anthraquinones，and free anthraquinones turned out to be 0.33%，1.86%，and 1.27%，separately.Thus，the content of tannins and bound anthraquinones was significantly reduced，while the content of free anthraquinones was significantly increased after the processing.The median lethal concentration 50(LC50) of three batches of Radix et Rhizoma Rhei before and after processing to zebrafish was 210.15 μg/mL，216.63 μg/mL，248.25 μg/mL，1 082.12 μg/mL，1 200.98 μg/mL，and 1 189.27 μg/mL，respectively.The LC50 of the water extract of the processed product increased significantly compared with that that of the raw product.The raw product induced different degrees of liver degeneration(hepatic atrophy，delayed absorption of yolk sac，liver cell enlargement，and tissue vacuolation).For the zebrafish treated with the processed product，only mild liver degeneration was observed in the zebrafish treated with high dose of processed product.Conclusion:In summary，the components of Radix et Rhizoma Rhei change remarkably and the hepatotoxicity significantly reduced after the processing.