Comparative genome analysis is performedbetween Shigella flexneri 2a strain 301 and its close relatives,the non-pathogenic E. coli K-12 strain MG1655. Resultshows that there are 136 DNA segments whose size is largerthan 1000 bp absent from Shigella flexneri 2a strain 301,which is up to 717253 bp in total length. These deleted segmentsaltogether contain 670 open reading frames (ORFs).Prediction of these ORFs indicates that there are 40% genesof unknown function. The other genes of definite functionsencode metabolic enzymes, structure proteins, transcriptionregulatory factors and some elements correlated with horizontaltransfer. Here we compare the complete genomicsequences of the two closely related species, which differ inpathogenic phenotype. To our knowledge, this not only revealsthe difference of genomic sequence between the twoimportant enteric pathogens for the first time, but alsoprovides valuable clues to further researches in its process ofphysiological activity, pathogenesis and the evolution of entericbacteria.