Objective To study the differential expression of serum proteins in concanavalin A(ConA) induced liver injury mouse model and analyze the relationship between disease progression and special proteins. Methods Twenty-five male mice were randomly divided into five groups, i.e. blank control group, phosphate-buffered saline (PBS) control group, liver injury groups developed 1, 3 and 6 h after ConA injection. The sera from all five groups were removed off the albumin by ProteoExtract~(TM)albumin removal kit. Then two dimensional electrophoresis ( 2DE) and mass spectrometry analysis were utilized to identify differences in protein expressions. Results Two specific proteins were detected in the liver injury group developed 6 h after ConA injection, which were identified as serum amyloid A-2 protein precursor and serum amyloid A-l protein precursor by mass spectrometry. Conclusions Serum amyloid A-2 protein precursor and serum amyloid A-l protein precursor are found at 6 h of ConA injection in ConA induced liver injury mouse model, which may be related to disease progression.