Nocardia seriolae is a pathogen that seriously harms Micropterus salmoides. To understand the drug resistance and the prevalence of drug resistance genes in N. seriolae in the main breeding area for Micropterus salmoides of Sichuan,20 strains of N. seriolae were isolated and identified from Sichuan from 2018 to 2019. Micro broth dilution method was used to determine the drug-resistant phenotype of the isolated strains. It was found that the sensitivity ratesof N. seriolae to doxycycline,tilmicosin,gentamicin,etc. were 100%,the drug resistance rates to penicillin,ceftiofur,cefoxitin,etc. were 100%,and the resistance rates to enrofloxacin and florfenicol were 45% and 20%,respectively. Ten strains showed multi-drug resistance,and the drug-resistant phenotypes of the isolates are different. The distribution of 78 drug resistance genes in 6 classes was detected by the ultra-high-throughput fluorescence quantitative PCR method. The results showed that all 6 classes of resistant genes could be detected in 20 isolates,the detection rate of tetA,tetG,tetS, aacC,acrA,acrB,floR and blaTEM reached 100%,and the detection rate of other resistance genes ranged from 5% to 95%,with regional and bacterial differences,indicating that the SichuanN. seriolae has the potential to evolve into multiple drug resistance.