Food animals may serve as a reservoir of bacteria that carry antimicrobial resistance genes that may be transferred to microorganisms found in humans and thereby limit the medical value of antimicrobials. In contrast to Escherichia coli from humans and several other animal species, there is little information on the frequency and mechanisms of antimicrobial resistance of that bacteria isolated from rabbits. The objective of the present study was to determine the antimicrobial resistance profile of 478 Escherichia coli isolates from healthy rabbits. Another objective was to assess the diversity and distribution of the major resistance genes [tetA, tetB, tetC, and tetM for doxycycline, bla(TEM), bla(OXA-1), bla(SHV), and bla(CTX-M-9) for amoxicillin, aac(3)II, aac(3)IV, and ant(2")I for gentamicin, and qnrA, qnrB, qnrS, aaC(6)Ib, and qepA for enrofloxacin], as well as the mutations in the quinolone resistance-determining region of the gyrA and parC genes, in these isolates. The percentage of isolates resistant to doxycycline was very high (89.3%). However, relatively few isolates were resistant to amoxicillin (16.1%), gentamicin (2.9%), and enrofloxacin (4.2%). Predominant resistance genes were tetA and tetB in the isolates resistant to doxycycline, and bla(TEM) in the isolates resistant to amoxicillin. Most Escherichia coli isolates with intermediate resistance to enrofloxacin presented a single mutation in gyrA, while most isolates resistant to it presented double mutations in gyrA and single mutations in parC, or double mutations in both gyrA and parC. The present study provides baseline data on frequency and molecular basis of antimicrobial resistance in Escherichia coli isolates from rabbits. In addition, the results of this study suggest that commensal Escherichia coli isolates from rabbits may be a reservoir of antimicrobial resistance genes.