Cronobacter sakazakii is an opportunistic foodborne pathogens involved in severe newborns infections, and subsequent pathogenic mechanism of C.sakazakii is poor understood.Lipopolysaccharide (LPS) is the important part of outer membrane of Gram-negative bacteria associated with virulence and host immune.Although the diversity of O-polysaccharide about LPS in C.sakazakii has been documented,Lipopolysaccharide-induced pathogenicity is largely unknown.In this study, Lipopolysaccharide was isolated from C.sakazakii, and then mice (w=20±3.6g) were infected using intraperitoneal injection.LPS-induced pathogenicity was determined through pathological change of intestinal tissue, varieties of pro-inflammatory factors, and expression abundance of iNOase, ZO-1, TLR2, TLR4.Finally, gut microbe changes were revealed by 16S rDNA sequencing.Results indicated Pathological change of intestinal tissue were observed in treated groups compared with control group.Inflammatory factors including NO, IL-1β, IL-6, and IL-10 were significantly increased with the increasing LPS concentrations, and the expression abundance of TLR4, TLR2,ZO-1, and iNOase at mRNA levels was up-regulated with increasing LPS concentrations.In addition, with the increasing of LPS concentrations, the number of bacteria colonies in blood was increased in 1d groups, indicating LPS contributes to translocation of bacteria.The findings suggested that LPS induced pathogenesis of C.sakazakii through myeloid differentiation primary response gene 88(MyD88)-dependent signaling pathway and changing structure of gut microbe.