[Objective] Ceftiofur was as the substrate to induce the standard strain of Escherichia coli(E.coli)to be the drug-resistance one.The resistant mechanism of E.coli to ceftiofur was studied.[Method] The sub-inhibitory concentration method was used to induce the standard strains C83907 and C83845.After they were induced for 10 generations,the double disc synergy test(DDST),NCCLS(National Committee for Clinical Laboratory Standards)confirmatory test and PCR amplification were used to detect the extend spectrum β-lactamases(ESBLs).The two fold dilution method was used to measure the minimal inhibitory concentration(MIC)of cetiofur to the strain which produced ESBLs.For the drug-resistance strain which produced ESBLs,the two fold dilution method was used to measure the minimal inhibitory concentrations of different proportions of cetiofur and tazobactam sodium.[Result] After they were induced 15 generations,MIC value of ceftiofur to the induced bacteria was during 8-10 μg/ml,and ESBLs was detected.MICs of cetiofur combining tazobactam sodium(the mass ratio was 1∶1-8∶1)to Escherichia coli produced ESBLs reduced 20-22 times than that of cetiofur.[Conclusion] The main mechanism of pathogenic Escherichia coli resistance to ceftiofur was that which produced ESBLs.