The widespread use of antibiotics in aquaculture has led to increasing problems caused by bacterial resistance. Given this, there is an urgent need to develop a medication regimen that prevents the formation of drug resistant bacteria. We estimated a number of pharmacodynamic (including mutant prevent concentration and mutant selection window)and pharmacokinetic parameters for the antibiotic drug enrofloxacin. Our objective was to develop a medication regimen against hemorrhagic septicemia in crucian carp(The minimal inhibitory concentration (MIC) was 0.125 μg/mL, the post-antibiotic effect (PAE) of enrofloxacin on the pathogenic bacterial strains was observed up to (1.67±0.42) hmutant prevention concentration (MPC) was 1.125 μg/mL, and the mutant selection window was between 0.125 and 1.125 μg/mL. We developed integrated enrofloxacin concentration-time curves for the serum of crucian carp following administration of a range of doses. Enrofloxacin persisted in the serum at concentrations above the MPC for 5 h at a dose of 5 mg/kg; 9.5 h at a dose of 10 mg/kg, and 23 h at a dose of 20 mg/kg. The serum PK/PD parameters AUC₂₄/MIC and /MIC were 137.22 and 15.05, respectively, at a dose of 5 mg/kg, 285.25 and 41.43, respectively, at a dose of 10 mg/kg, and 426.25 and 52.32, respectively, at a dose of 20 mg/kg.The drug remained in the plasma with a concentration >MPC for (24-PAE) h and AUC24/MICemorrhagic septicemia can be controlled , at intervals of 24 h.The proposed withdrawal time in crucian carp should not be less than 25 d. The methods described in this study also can be used for developing dose guidelines for other anti-bacterial drugs to prevent selection for drug-resistance.