To study the anti-coagulant effect and influence of danggui Sini decoction (DSD) on rat's plasma endogenous metabolites by animal experiment and ¹H-NMR based metabolomics method. After intragastric administration of Danggui Sini Decoction for 7 days, Plasma thrombin time (TT) was measured. Rat plasma metabolic fingerprint in two groups was analyzed using ¹H-NMR, based on which the principal component analysis( PCA) and orthogonal partial least-squares discriminant analysis(OPLS-DA) models for metabonomic analysis. Potential biomarkers were screened by using variable importance in the projection (VIP) and T test. DSD could prolong TT of the rat significantly (P < 0.05). Compared with control group, six kinds of endogenous metabolites in DSD group change significantly (P < 0.05), among which isobutyrate, carnitine and phenylalanine content had an upward trend (P < 0.01) and lysine, Histidine and cholesterol content had a downward trend (P < 0.05). It is likely that carnitine, phenylalanine, Histidine and cholesterol are the potential metabolic markers in the anti-coagulant process and DSD affects the platelet aggregation and the expression of tissue factor and fiber protease by regulating the energy, amino acid and lipid metabolism.