To explore the mechanisms and key metabolites of a chronic blood stasis syndrome model in rats induced by different doses of epinephrine through metabolomics.Methods:The chronic blood stasis syndrome model was established by continuous subcutaneous injection of different doses of epinephrine.Hemorheological parameters and coagulation indicators were measured to assess the model.Detection was performed using reverse-phase liquid chromatography-tandem mass spectrometry(RPLC-MS) and hydrophilic interaction liquid chromatography-mass spectrometry(HILIC-MS).Partial least squares discriminant analysis(PLS-DA) was used to analyze the changes in endogenous metabolites before and after administration.Results:Compared with the normal control group，the high-，medium-，and low-dose epinephrine groups showed significant increases in whole blood viscosity at different shear rates，elevated prothrombin time and fibrinogen levels in the coagulation profile，and decreased body weight.Metabolomics analysis revealed clear differentiation between the normal control group and the high-dose epinephrine group.The separation trend was closely related to the dosage.Metabolites such as glucose，acetyl-CoA，and eicosapentaenoic acid were identified in the RPLC-MS mode，while metabolites such as taurine and oleic acid were detected in the HILIC-MS mode.Twenty-eight potential biomarkers associated with the pathogenesis and progression of qi stagnation and blood stasis syndrome were identified in both modes.Conclusion:A certain dose of epinephrine can induce chronic blood stasis syndrome，and the modeling degree varies with the dosage.Metabolic changes related to glucose metabolism，fatty acid metabolism，bile acid metabolism，carnitine metabolism，and tryptophan and tyrosine metabolism may be involved in the mechanism and progression of chronic blood stasis syndrome based on the correlation with the dosage-related changes in the body.