This study aims to investigate the differences of in vitro pharmacodynamics(PD)parameters and in vivo pharmacokinetic(PK)of florfenicol in crucian carp(Carassius auratus)and grass carp(Ctenopharyngodon idella)against a pathogenic Aeromonas hydrophila strain(CAAh01),which were used to draw reasonable medication regimen to control disease and prevent drug resistant bacteria.The pharmacodynamics of florfenicol on bacterium CAAh01 were studied in vitro and the pharmacokinetic parameters of florfenicol in crucian carp and grass carp were monitored after a single oral gavage of 10,20,30 mg per kg body weight to determine a medication regimen to prevent bacterial sepsis in grass carp and crucian carp.The in vitro pharmacodynamic results showed that MIC of florfenicol on CAAh01 was 0.5 μg/mL,and MBC was 1.0 μg/mL; the MPC was 6.0 μg/mL(12MIC); the mutant selection window(MSW)of florfenicol on the pathogenic bacterial strains was 0.5-6.0 μg/mL.The time of florfenicol concentration in serum of crucian carp above MPC was 5h at the dosage of 10 mg/kg; 8 h at the dosage of 20 mg/kg,24 h at the dosage of 30 mg/kg,respectively;AUC₂₄/MIC and C_max/MIC of florfenicol in serum were 177.06 and 15.59 at the dosage of 10 mg/kg,respectively; 265.90 and 21.32 at the dosage of 20 mg/kg,respectively; 426.50 and 31.24 at the dosage of 30 mg/kg,respectively.The time of florfenicol concentration in serum of grass carp above MPC was 0h at the dosage of 10 mg/kg and 20 mg/kg,3h at the dosage of 30 mg/kg,respectively;AUC₂₄/MIC and C_max/MIC of florfenicol in serum were 38.60 and 4.75 at the dosage of 10 mg/kg,respectively; 75.08 and 10.08 at the dosage of 20 mg/kg,respectively; 121.94 and 19.99 at the dosage of 30 mg/kg,respectively.Considering the drug remained in the plasma with a concentration above MPC and AUC24/MIC≥100 or C_max/MIC>8,florfenicol is determined to be applicable for the prevention and treatment of bacterial diseases of crucian carp.The recommendation of the dosing regimen to prevent the selection of drug-resistance is 30 mg/kg,at the intervals of 24 h for 1 day,and the proposed withdrawal period should not be less than 20 d.However,it is not suitable to be used continuously to control and treat bacterial diseases in grass garp.