Abstract: This study aims to analyze synergistic effects and synergistic mechanism of nisin and HPP(high pressure processing)on the inactivation of Escherichia coli O157:H7. The Gram-negative bacteria E. coli was used as target bacteria,and the concentration of Nisin was 0.005% or 0.01%,the pressure level of HPP was 350 MPa,and the treatment time was 2 min. The external morphology and internal structure of E. coli cells were observed by scanning electron microscopy(SEM)and transmission electron microscopy(TEM). The cell membrane permeability was detected by laser confocal microscopy(CFM)and flow-cytometry(FCM). The results showed that,comparing with the separate ultra high pressure treatment,0.005% or 0.01% nisin combined with 350 MPa/2 min ultra-high pressure had a significant synergistic bactericidal effect on E. coli,which bacterial colonies counts reduced by 6lg~8lg,and with no changes on cell shape,while the cell membrane and interior organization were badly destroyed. The bacteria with intact cell membrane only accounted for 2.13%~5.68% of the total,more endosomal leakage and more cavities appear in the cell. All the data suggested that Nisin and HPP exhibited synergistically bactericidal effects on this strain. The possible mechanism was assumed that HPP firstly damaged the outer membrane of E. coli cells,and then nisin attacked the membrane of these cells,which caused the leakage and hollow organs.