The pharmacokinetics of ceftiofur were studied in 78 catfish divided into 3 groups following IV and IM (single and repeated) administrations. Following a single IV injection of 5 mg/kg body weight of ceftiofur in normal catfish (Clarias lazera), serum concentration-time curve was best described by a two compartments open model with elimination half  life (t0.5β), volume of distribution (Vdss) and total body clearance (CLtot) of 5.700 h, 229.71 ml/kg and 0.642 ml/kg/min, respectively. Following a single IM administration of 5 mg ceftiofur /kg body weight in normal catfish (Clarias lazera) ,  the peak serum concentration (Cmax) was 21.77 µg/ml, achieved at a maximum time (Tmax) of 2.15 h. The mean systemic bioavailability was 67.22%. The serum concentrations of ceftiofur following repeated IM administration of 5 mg/kg body weight once daily for five consecutive days in healthy and experimentally Aeromonas hydrophilia infected catfish (Clarias lazera) showed a lower significant values recorded in experimentally Aeromonas hydrophilia infected catfish (Clarias lazera) than in normal ones. Ceftiofur showed accumulative behavior in serum of fish. Results of this study indicated that ceftiofur was useful for treatment of Aeromonas hydrophilia infections in fish. Ceftiofur was assayed in serum, liver, kidney, dorsal muscle, abdominal muscle and skin after 24, 48, 72, 96 and 120 h from the last daily dose of 5mg ceftiofur/kg body weight for five days. . Ceftiofur could not be detected by spectrophotometer assay in all tested tissues in normal fish except in liver (four days), kidney (four days), and dorsal muscle (four days) post last administrations.  Ceftiofur was completely cleared from serum and tissues at five days after the stoppage of drug dosage but in experimentally infected fish Ceftiofur could not be detected in all tested tissues except in liver (three days) and kidney (three days) post last administrations. Ceftiofur was completely cleared from all tissues at (four days) after the stoppage of drug dosage