Abstract: Objective To study the molecular characteristics and antibiotic resistance of Salmonella diarrhea cases in sentinel hospitals through active surveillance system conducted by public health laboratory. Methods Two sentinel hospitals were chosen for collection of stool specimens from food-borne infectious diarrhea cases and for Salmonella separation and detection immediately following serotyping and antimicrobial susceptible test (AST) on those isolates. Moreover, pulsed field gel electrophoresis (PFGE) was used for the genetic homology analysis. Results A total of 2 579 diarrhea specimens were collected and analyzed from 2010 to 2012, with 185 Salmonella isolates, covering 23 different serotypes (annual positive rates were 9.1%, 6.8%, 5.1%, with an average 7.2%). Salmonella enterica serovar Enteritidis(S. Enteritidis) and Typhimurium(S. Typhimurium) were the most common serotypes, of which 68.9% cases were seen in those aged 21 to 60 and 21.4% cases in those over 60 years old. 27.7%-96.9% S. Enteritidis and 2.6%-63.2% S. Typhimurium(P all<0.05) proved resistant to Nalidixic acid,Sultisoxazole, Streptomycin, Sulfamethoxydiazine, Gentamicinand Tetracycline. PFGE analysis on 22 S. Enteritidis strains showed 11 different clusters, while 20 S. Typhimurium strians showed 6.Conclusion S. Enteritidis and S. Typhimurium are the most common Salmonella serotypes, and molecular typing indicates the existence of clustering and sporadic outbreaks caused by dominance clones. We should be alert to early warnings on potential outbreaks of multiple-drug-resistant (MDR) S. Enteritidis. Active surveillance system based on public health laboratory should play an important role in the control of food-borne infectious diseases.