Abstract: In order to study the resistance of geese and fish-derived Escherichia coli（E.coli）to 12 kinds of antibiotics for poultry and livestock, the test conducted a drug resistance study on the isolated goose and fish-derived E.coli（50 strains each）. Sterile suspensions of norfloxacin, florfenicol, gentamicin, spectinomycin, tilmicosin, tylosin, chlortetracycline, tetracycline, amoxicillin, doxycycline, enrofloxacin and trimethoprim（TMP）,were prepared using micro-membrane filtration method; the drug resistance of E.coli to 12 kinds of livestock and poultry antibiotics was determined by 96-well plate culture method, and the drug resistance rate was counted and the drug resistance spectrum was analyzed. The results showed that 100 strains of E.coli were resistant to 12 kinds of antibiotics for poultry and livestock; the resistance rate of goose-derived E.coli was 46%-100%,and the resistance rate of fish-derived E.coli was 86%-100%. At the same time, geese and fish-derived E.coli showed difference in resistance to the same antibiotics for poultry and livestock; among them, the biggest difference was florfenicol（the difference in resistance rate was 48 percentage points）,followed by gentamicin, norfloxacin and tetracycline. The multi-drug resistance of E.coli from fish to 12 kinds of poultry and animal antibiotics ranged from 9 to 12.The multiple drug resistance of E.coli from geese to 12 kinds of poultry and animal antibiotics ranged from 7 to 12.The results suggested that fish and goose-derived E.coli were resistant to 12 kinds of antibiotics for livestock and poultry, and drug-resistant spectrum were wide.