Abstract: Objective To search for the new proteins related to multidrug resistance,the proteomics of whole cellular proteins between sensitive strain and induced anti-multidrug strain of shigella flexneri by using of two-dimensional electrophoresis(2-DE)were compared.Methods Clinical sensitive shigella flexneri strain was induced into anti-drug strain by 1/2 MIC induced trials of four kinds of antibiotic;Immobilized p H gradient(IP G)two-dimensional electrophoresis was adopted and the gels were analyze by Image Master 2D Platinum software;Matrix assisted laser desorption/ionization-time of flight mass spectrometry(MALDI-TOF MS)were used to analyze differential expression proteins.Results Induced anti-multidrug strain of shigella flexneri was obtained successfully.It was found that there were(946±37)protein spots in whole cellular protein 2-DE gels of sensitive strain and(1 096±189)protein spots in that of induced anti-multidrug strain,48 differential expression protein spots were found and 5 proteins related to multidrug resistance were identified based on peptide mass fingerprinting:A TP binding cassette transporter protein,γ-glutamyltranspeptidase,aspartate carbamoylransferase were high expression in induced anti-multidrug strain;But chain elongation factor EF-Tu and SSB were high expression in sensitive strain.Conclusion By mass spectrum analysis of 5 proteins related to multidrug resistance,some important cellular metabolism enzymes expressed highly,ATP binding cassette transporter protein affected seriously the mechanism of shigella flexneri multidrug resistance.