Nocardia seriolae is a pathogen that seriously harms Micropterus salmoides. In order to understand the drug resistance and the prevalence of drug resistance genes in N. seriolae, the main breeding area for Micropterus salmoides in Sichuan, 20 strains of N. seriolae were isolated and identified from Sichuan from 2018 to 2019 in the study. The micro broth dilution method was used to determine the drug-resistant phenotype of the isolated strains. It was found that the sensitivity rates 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, among them, 10 strains showed multi-drug resistance, and the drug-resistant phenotypes of the isolates are different. This result provides a reference for the effective medication of Sichuan N. seriolae. The ultra-high-throughput fluorescence quantitative PCR method detected the distribution of 78 types of drug resistance genes in 6 types of isolates. The results showed that all 6 types of resistant genes could be detected in 20 isolates. including, and. 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%. There were strain differences in drug resistance genes detection, indicating that the Sichuan N. seriolae has further evolved into a multi-drug resistant bacteria potential risks.