OBJECTIVE：To study inhibitory activity of different extracts of Dracocephalum moldavica to clinical pathogenic bacteria，and to excavate its possible antibacterial mechanism. METHODS ：After extraction by 65％ ethanol and extraction by petroleum ether ，dichloromethane，ethyl acetate ，n-butanol，the different polar fractions of D. moldavica were obtained . Taking Klebsiella pneumoniae ，Staphylococcus aureus and other clinical multiple resistant pathogens as objects，the diameter of inhibition zone of different extraction fractions was measured by paper diffusion method ，and the antibacterial active fraction was screened. The minimal inhibitory concentration （MIC）of antibacterial active fraction to common clinical pathogens was determined by agar dilution method ；the growth curve of MRSA was drawn by turbidimetric method. The differentially expressed protein between antibacterial active fraction group and control group was screened by PEAK ® Q 8.5 software，and the gene ontology （GO）analysis and KEGG signaling pathway enrichment analysis were carried out by Blast 2 GO and KOBAS 3.0 online software. RESULTS ： Petroleum ether ，dichloromethane，ethyl acetate and n-butanol fraction of D. moldavica had no significant inhibitory effect on Gram-negative bacteria. The ethyl acetate fraction of D. moldavica had antibacterial activity in varying degrees against several kinds of Gram-positive bacteria as Staphylococcus aureus ，S. epidermidis；the diameter of inhibition zone was 10-16 mm，which was the active fraction. MICs of ethyl acetate fraction to S. aureus ，S. epidermidis and S. hominis were all 0.781 3 mg/mL；MIC to S. saprophyticus was 0.390 7 mg/mL；MICs to S. saprophyticus and standard strain of S. aureus were both 1.562 5 mg/mL. The 1， 2 times MIC of ethyl acetate could inhibit the growth of MRSA ，and the inhibitory activity increased with the increase of dose. A total of 300 differentially expressed proteins were screened （P＜0.01），of which 239 were up-regulated and 61 were down-regulated. The differentially expressed proteins were （No.81260478，No.816- mainly concentrated in cell sites such as cells ，cellular com- 60048） ponent，etc.，and in metabolic process such as cell process ， biological process and molecular functions such as catalytic activity，protein binding ，etc. They were mainly concentratedwang.zhanli@hotmail.com in microbial metabolism in different environments ，fructose and mannose metabolism signaling pathway （P＜0.05）. CONCLUSIONS ：The ethyl acetate fraction of D. Moldavica is the antibacterial active fraction ，and its activity may be related to the microbial metabolism and cell glycometablism.