Abstract： Objective To review the basic clinical characteristics and the pathogens and their antimicrobial susceptibilities to neonatal sepsis in very low birth weight infants (VLBWI) and extremely low birth weight infants ( ELBWI) for selection of appropriate antibiotics. Methods A retrospective chart review of 56 cases with neonatal sepsis(early onset neonatal sepsis 3 cases, late onset 53 cases) in VLBWI and ELBWI admitted to the neonatal intensive care unit of Yuying Children's Hospital of Wenzhou Medical College from January 1, 1999 to December 31, 2008 was conducted. The basic clinical characteristics and the results of blood culture and antimicrobial susceptibilities were analyzed. Results Among the 56 cases, the clinical presentations were non-specific. A total of 43 strains of bacteria were isolated, and the most important pathogens responsible for neonatal sepsis in VLBWI and ELBWI were opportunistic pathogenic bacteria. In early onset neonatal sepsis, there was only one culture-proven sepsis that was Chryseobacterium meningosepticum. In the late onset neonatal sepsis cases, the main pathogens of Gram-negative organisms were Klebsiella pneumoniae (33. 3%, 14/42), and the most common Gram-positive organisms were coagulase-negative Staphylococci (26. 2%, 11/42), followed by Enterococcus species (11. 9%,5/42). Furthermore, there were 2 fungal sepsis(4. 8%, 2/42), which were infected by Candida albicans. All of the coagulase-negative Staphylococci were methicillin-resistant coagulase-negative Staphylococci, and they were resistant to common antibiotics and sensitive to vancotnycin and rifampicin. And all of the Klebsiella pneumoniae produced extended-spectrum (Hactamases, which were sensitive only to a few antibiotics such as carbopenems, aminoglycosides and quinolones. Among those 56 cases, 43 patients were cured, 13 died, including six patients who refused any treatments, the mortality rate of neonatal sepsis in VLBWI and ELBWI was 23. 2%. Conclusions The clinical presentations of neonatal sepsis in VLBWI and ELBWI were non-specific, and the most important pathogens were opportunistic pathogenic bacteria, which were multi-drug resistant. Routine blood culture should be taken from infants who are suspected of neonatal sepsis and empirical use of appropriate antibiotics should be initiated as soon as the blood specimen for culture has been drawn. To reduce the occurrence of multi-drug resistant bacteria, we should restrict the use of antibiotics especially the third generation of cephalosporins in neonates as much as possible.