Abstract: Objective To investigate the major serotypes and drug resistance of Shigella isolated from sick children with diarrhea in Xiaoshan, Zhejiang province, and provide evidence for rational use of antibiotics and diarrhea prevention. Methods The biochemical identification, serotyping and drug susceptibility test were conducted for the strains of Shigella isolated from diarrhea children in our hospital from January 2006 to December 2011, and the data were analyzed with WHONET 5.6 Software. Results Among 318 strains of Shigella isolated, 221 were Shigella sonnei (69.5%), 96 were Shigella flexneri (30.2%), only 1 was Shigella boydii (0.3%). Totally 200 strains (62.9%) were detected in age group 5years, the resistance rate to ampicillin was highest (97.1%),followed by trimethoprim-sulfamethoxazole (TMP/SMZ) (88.8%) and cefotaxim (44.7%). No strain was detected to be resistant to cefoperazone/sulbactam, imipenem and meropenem. The resistance rates of Shigella flexneri to ciprofloxacin and levofloxacin were 44.8% and 33.3%,but no Shigella sonnei strain was detected to be resistant to fluoroquinolones. The differences in the resistance rates to piperacillin, ceftazidime, cefepime, TMP/SMZ and fluoroquinolones between Shigella flexneri and Shigella sonnei had statistical significance (P0.01). Conclusion The major pathogen to cause diarrhea in children was Shigella sonnei in Xiaoshan, Penicillin and TMP/SMZ are not suitable for the clinical treatment. Enzyme inhibitors is the first choice for the treatment of Shigella infection. The resistant rate of Shigella to piperacillin, cefotaxime, ciprofloxacin and levofloxacin showed an upward trend.