OBJECTIVE： To analyze the distribution and drug resistance of pyogenic encephalitis in our hospital， and to provide reference for rational use of antibiotics. METHODS： The cerebrospinal fluid pathogen of 4 255 patients with pyogenic encephalitis in our hospital during Jan. 1st， 2011-Dec. 31st， 2014 were cultured and identified， and drug sensitivity test was conducted. RESULTS： A total of 834 pathogens were isolated with positive detection rate of 19.6％， including 576 strains of gram-positive bacteria， accounting for 69.1％； 255 strains of gram-negative bacteria， accounting for 30.6％； 3 strains of fungi， accounting for 0.4％. Top 3 gram-positive bacteria were Coagulase-negative staphylococci （436 strains）， Staphylococcus aureus （56 strains） and Enterococcus （29 strains）. Top 3 gram-negative bacteria were Klebsiella pneumoniae （46 strains）， Acinetobacter baumannii （38 strains） and Escherichia coli （31 strains）. Top 3 departments were neurosurgery department （506 strains）， ICU （169 strains） and severe respiratory disease department （64 strains）. Results of drug sensitivity test showed that no drug-resistant Staphylococcus and Enterococcus strains to vancomycin， teicoplanin and miuocycline was found； nonfermenting Gram-negative bacilli showed low resistant to minocycline. CONCLUSIONS： Gram-positive bacteria dominates the detection rate of cerebrospinal fluid of pyogenic encephalitis patients； drug resistance of various pathogens is serious and clinicians should choose antibiotics based on drug sensitivity.