We investigated the resistance of avian Escherichia coli to commonly used clinical antibiotics in Hebei Province. It is of significance to reveal the extent and mechanism of drug resistance, as well as to prevent and control colibacillosis. We investigated the resistance of 132 E. coli isolates to 5 kinds of antibiotics (including β-lactams, aminoglycosides, tetracyclines, sulfonamides, and chloramphenicol) using the Kirby-Bauer drug susceptibility test, and resistance genes were detected by PCR. The results showed that the E. coli had a higher resistance rate to ampicillin, cephalotin, gentamicin, streptomycin, tetracycline, doxycycline, sulfamethoxazole trimethoprim, sulfamonomethoxine, and florfenicol, but it had higher sensitive rate to cefepime, imipenem, spectinomycin, and minocycline. Of the resistance genes, the TEM, aac(3)-IIa, tetA, Sul1, Sul2, and forl had higher positive rates. Therefore, drug resistance of avian E. coli in Hebei Province is very serious. The resistance mechanisms may include structure changes of the target enzyme mediated by multiresistance genes, and resulting in reduced affinity and increased efflux of antibiotics.