Abstract: To investigate the antibacterial activity of artesunate（ASN） alone or in combination with cephalosporins on multidrug-resistant（MDR） Klebsiella pneumoniae, a total of 32 strains of multidrug-resistant K. pneumoniae isolated from the Changsha Central Hospital were collected in 2018 and divided into separate drug groups: artesunate（ASN） groups, ceftriaxone sodium（CRO）/ceftazidime（CAZ） groups and combined application groups. The effect of artesunate combined with cephalosporins on the growth of multidrug-resistant K. pneumoniae was observed by the method of bacterial dynamic growth curve. The antibacterial effect of artesunate alone or in combination with cephalosporins on multidrug-resistant K. pneumoniae was determined by the method of micro-broth dilu tion. The expression level of AcrB mRNA and its regulatory genes MarA and AcrR mRNA were detected by RT-PCR.The results showed that the final concentration of 2 048 μg/mL ASN combined with ceftriaxone sodium or ceftazidime significantly inhibited the growth of multi-drug resistant K. pneumoniae, and the curve was gentle; the final concentration of 1024 μg/mL ASN combined with ceftriaxone sodium or ceftazidime was significantly lower the MIC50 of multidrug-resistant K. pneumoniae than the drug-administered groups（K=68.07, P＜0.05; K=62.34,P＜0.05）. 1 024 μg/mL ASN combined with ceftriaxone sodium or ceftazidime were mainly additive; when 2 048 μg/mL artesunate was combined with ceftriaxone sodium or ceftazidime, the expression of AcrB in the efflux pump gene was inhibited. when 2 048 μg/mL artesunate combined with 512 μg/mL ceftri ax one sodi um significantly inhibited the expression of the positive regulator MarA, but had no significant effect on the expression of the negative regulator AcrR. Artesunate significantly improved the sensitivity of multidrug-resistant K. pneumoniae to ceftriaxone sodium and ceftazidime, and its mechanism may be related to the down-regulation of the expression of the efflux pump gene AcrB.