Abstract: The protein expression of tilapia liver in different periods was studied after Streptococcus agalactiae infection.Two-dimensional electrophoresis was employed to analyze the proteome from liver of GIFT tilapia at 0 h,24 h,48-144 h and 12 days after Streptococcus agalactiae infection.The differential expressing proteins were identified by mass spectrometry.The results show that there were significant differences between experimental groups and control group in the proteomic map.Among the 30 differentially expressed proteins,13 show an up -regulated expression and 15 shows down- regulated expression.Two proteins disappeared in the infection group 12 days later.The function classification of these proteins was analyzed by MALDI-TOF/TOF 4800 and mascot soft ware.They included association with energy metabolism proteins,cell defense and stress proteins,digestive immune proteins,immune and detoxification and other proteins.It is likely that they play an important role in the resistance responses toStreptococcus agalactiae.The discovery and identification of these proteins can offer a valuable insight into Tilapia Streptococcus lactis vaccine development and disease resistance breeding.