〔Abstract〕 Objective To investigate the drug resistance and pathogenicity of six clinical isolates ofKlebsiella pneumoniae(Kp), and to provide a basis for prevention and treatment of Kp infection. Methods The six strains from different hospitals were isolated, cultured, and identified by species-specific genekhe. Their whole genome sequences(WGS) were obtained using next-generation sequencing technology(NGS). Based on the WGS, the capsular serotypes, sequence types(ST) and drug-resistance genes of six strains were identified. The capsular serotype genes and virulence genes were validated or identified using PCR. Broth microdilution tests were conducted to validate their drug susceptibility, and mice were challenged with Kp aerosols by MicroSprayer aerosolizer to evaluate their pathogenicity. Results The six strains were all serotype K2 but belonged to four ST types(ST14, ST65, ST700, and ST86), and collectively carried six virulence genes and 23 drug-resistance genes. All the six strains were resistant to ampicillin, but only one strain was multidrug-resistant. Four strains exhibited high mucoid characteristics. Five strains could cause mortality in mice, which were preliminary identified as high virulence strains. Conclusion For the six Kp clinical isolates from different sources, only one strain named NY 13294 is both multidrug-resistant and highly virulent, and other four highly virulent strains are resistant to one or two types of antibiotics.