Objective To compare of the spectra of human serum proteins on two-dimensional gel electrophoresis before and after liver transplantation for studying the mechanism of the immune rejection and immune tolerance after human liver transplantation. Methods Highly abundant proteins in serum were preprocessed using aurum serum protein mini kit and were separated by 2-DE.The spectra were analyzed by using Image Master 2D Platinum software. Results The 2-D spectra of human serum proteins before and after liver transplantation 24h, 10d and 30d were established. Among them 15 protein spots had significant change, 14 protein were up-regulated and one protein was down-regulated. Conclusions Proteomics of human serum after liver transplantation is initially established. The discovery of differentially expressed proteins may provide further insight into molecular mechanisms of immune rejection and immune tolerance.