Objective To investigate the distribution and drug resistance of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates, so as to provide guidance for reasonable use of antibiotics. Methods Clinical CRKP isolates were collected in Changhai Hospital of Naval Medical University (Second Military Medical University) from Jan. 2014 to Dec. 2017, and the antimicrobial susceptibility test was carried out using automated instrument method and Kirby-Bauer method. The results were interpreted according to the standards of America Clinical and Laboratory Standards Institute (CLSI) or America Food and Drug Administration (FDA), and the data were analyzed by WHONET 5.6 software and SPSS 20.0 software. Results A total of 403 clinical CRKP isolates were collected, and 169 (41.9%) strains of CRKP were isolated from the specimens obtained from sputum/bronchoalveolar lavage fluid. The first isolation of CRKP was from different specimens, and there was a significant difference in the incidence of CRKP blood flow infection (P<0.05). The top 3 departments in terms of isolation rates were Burn Intensive Care Unit (30.0%, 121/403), Digestive Department (8.4%, 34/403) and Emergence Intensive Care Unit (7.2%, 29/403). The antimicrobial susceptibility test showed that the drug resistance rate of the CRKP strains was more than 60.0% to all antibiotics, but tigecycline and fosfomycin. Conclusion The CRKP isolates are resistant to most commonly used antibiotics. It is necessary to strengthen the surveillance of drug resistance of CRKP isolates and take effective measures to control the spread of CRKP, especially in departments such as Burn Intensive Care Unit.