Abstract: To investigate the bacterial infection of diarrhea poultry in large-scale poultry farms in Leizhou city, Leizhou Peninsula, more than 20 samples（spleen, liver, pericardial fluid） were isolated and cultured, examined by Gram staining, screened by McConkey and eosin-methblue medium. Further biochemical tests and 16S rRNA identification were carried out to determine the species of the selected pathogens. Finally, drug susceptibility tests and animal regression tests were carried out. The results showed that 31 strains of E. coli and 10 strains of Salmonella were isolated from the samples. The sensitivity rate of isolated E. coli to polycolistin B was only 58.0%; the sensitivity rate to cefotaxime was 100%, and the resistance rate to other 14 drugs was between 67.7%-100%. The susceptibility rates of Salmonella to ciprofloxacin, polymyxins and cefotaxime were 50.0%, 80.0% and 100%, respectively, and the resistance rates to other 13 drugs ranged from 50.0%-100%. Both E. coli and Salmonella were pathogenic to the ducklings. The liver and spleen were enlarged with white necrotic spots and necrotic foci on the surface. In conclusion, polycolistin B and cefotaxime could be selected to control the infection of pathogenic E. coli and salmonella in large-scale poultry farms in Leizhou, Leizhou Peninsula.