Aim of the study was to evaluate the effect of quercetin and enrofloxacin with/without quercetin on elimination of pathogen Escherichia coli O78/H12 in infected chickens. Effect of quercetin on disposition of enrofloxacin was investigated and Pharmacokinetic-pharmacodynamic indices were calculated. Enrofloxacin was absorbed after oral administration in infected animals but with large inter-individual variations. Low concentrations of its main metabolite, ciprofloxacin, were found which could be explained with marked reduction of enrofloxacin transformation in infected animals. Quercetin significantly decreased bioavailability of enrofloxacin and its transformation to ciprofloxacin. Lower formation of metabolite was also found in the studied tissues as spleen, heart, lungs and in liver of group treated in combination with quercetin. Results in infected and quercetin (50 mg/kg) treated group shows lower percentage of re-isolates of the pathogen bacteria in comparison to infected and untreated animals, and close to the low dose (10 mg/kg) of enrofloxacin. High dose of enrofloxacin given in a short time in an infection model with high inoculum size, resulted in better eradication of bacteria although re-isolates could be found in spleen. Additional improvement of the outcome of fluoroquinolone therapy could be searched in early start of drug administration according to the terms of metaphylaxis.