Objective To compare the effect of peeling on the chemical compositions and potential hepatotoxicity of the water extract of Polygonum multiflorum Thunb.(Heshouwu).Methods The chemical constituents of water extract of peeled Heshouwu,and water extract of peels were analyzed by UPLC-Q-TOF-MS,before the identification.Multivariate statistical analysis was used to compare the levels of hepatotoxic constituents in different parts of Heshouwu.Totally 40 male SD rats were selected and randomly divided into a normal group,a water extract of unpeeled Heshouwu group and a water extract of peeled Heshouwu group.The rats in each treatment group were orally given a dose of 20 g·kg-1(calculated according to the amount of unpeeled Heshouwu materials),while the rats in the normal group were orally given an equivalent volume of deionized water once daily for 35 consecutive days,before the serum and liver samples were collected.Serum biochemical analysis and liver pathology were used to compare the liver injury in each group,while metabolomics was used to compare the level of liver injury biomarkers of rats in each administration group.Results Totally 190 chemical constituents were identified in Heshouwu.Peeling significantly reduced the levels of hepatotoxic constituent 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside and potentially hepatotoxic constituent dimer of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside,as well as anthraquinones in the water extract of Heshouwu.Peeling also obviously alleviated the liver pathological damage of Heshouwu to rats.Metabolomic analysis showed that peeled Heshouwu greatly reversed the levels of endogenous liver injury biomarkers such as docosahexanoic acid,pipecolinic acid,glycohyocholic acid,tyrosine and reduced glutathione in rats compared with unpeeled Heshouwu.Conclusion Peeling can reduce the hepatotoxic constituents of stilbene glycosides and anthraquinones in the water extract of Heshouwu and may reduce the hepatic pathological damage effect of Heshouwu by attenuating the perturbation of endogenous liver injury biomarkers.This study provides a scientific basis for the standardisation Heshouwu processing.