Abstract： Objective:To study the effect of hyperbaric oxygen (HBO) treatment on reversing the drug resistance of Klebsiella pneumoniae against the third and the fourth generation of cephalosporins and its mechanism.Methods:Three strains of Klebsiella pneumoniae, collected in the Department of Respiratory and Critical Care Medicine of Jining No.1 People′s Hospital from the January of 2017 to the December of 2017, were used in this study, which all showed positive with cephalosporinase (AmpC) and extreme spectrum β -lactamase (ESBLs). The 3 bacterial strains were identified by VITEK microbial identification system, divided equally into control group and HBO group, and incubated with the third and the fourth generation of cephalosporins in different concentrations. The minimum inhibitory concentration (MIC) was determined by the two-fold agar dilution method, and the strains activity was determined by the plate counting method. In addition, the total protein in the strains was extracted, and the expression of HIF-1α was detected by using Western blotting method. The three-dimensional test of ceftazidime and cefpirome and the disc diffusion confirmatory method were used to detect AmpC and ESBLs in the strains, respectively.Results:Compared with the control group, the MIC values of the third and the fourth generation of cephalosporins, stain activity, and the expression of HIF-1 were all reduced in the HBO group( P<0.05). In addition, the HBO treatment significantly reduced the detection rates of AmpC and ESBLs. Conclusion:HBO treatment can significantly reverse the drug resistance of Klebsiella pneumoniae to the third and the fourth generation of cephalosporins, which may be related to the inhibition of the HIF-1 pathway and the reduction of AmpC and ESBLs.