In this study, a physiologically based pharmacokinetics (PBPK) model was firstly developed for danofloxacin in healthy broiler chickens after a single oral administration at 5 mg/kg bw. Then, the model extrapolation from healthy chickens to those infected with Pasteurella multocidaones was performed. The healthy model was validated through a comparison of predicted and previously published concentrations, which indicated that the healthy PBPK model had good predictive ability in plasma, lung, muscle, liver, and kidney, especially at the later sampling time points. Multiple dosing of administration was incorporated into the healthy and infected models. In addition, a Monte Carlo simulation (MCS) included 1000 iterations was further incorporated into both models to predict the withdrawal times of danofloxacin in healthy and infected chickens, which were estimated to be 3 and 2 days, respectively.