Abstract: Study on the interaction of the absorbed soyasaponin Ⅱ with human serum albumin( HSA) in the circulatory system was performed. The binding of soyasaponin Ⅱ to the protein was characterized by circular dichroism spectrometry,intrinsic fluorescence spectrometry and molecular. CD spectra displayed that with the concentration ratios of 1 ∶ 2 and 1 ∶ 4, alpha helical contents of HSA increased and the beta sheet contents decreased. Fluorescence spectra showed that the 3D structure of albumin after the binding of soyasaponin Ⅱwas changed. The molecular modeling revealed that the binding forces of soyasaponin Ⅱ to HSA were mainly hydrogen bond and hydrophobic interactions. Glc A and Rha parts of soyasaponin sugar chains and amino acid residues,including Glu153,Ser192,Gln196,Glu450,Asp451 and Ser454,formed hydrogen bonds. The aglycone of soyasaponinⅡhad the hydrophobic interaction with HSA,amino acid residues of which were mainly Leu,Val,Ala and Trp.