The pharmacokinetic parameters of cefotaxime were studied following I.V. and I.M. (single & repeated) injection in normal and   experimentally Staphylococcus aureus infected broiler chickens. Following a single intravenous injection of 25 mg cefotaxime/kg b.wt in normal chickens, cefotaxime could be detected therapeutically for 12 hours post intravenous injection with mean value 2.34 µg/ml.  The serum concentration – time curve of cefotaxime following intravenous injection showed that the drug obeyed two compartments open model with elimination half- life (t0.5(β) =3.11 h), volume of distribution (Vdss = 496.90 ml/kg) and total body clearance of the drug (CLtot= 137.63 ml/hr/kg). Following a single intramuscular injection of 25 mg/kg body weight cefotaxime in normal chickens, the peak plasma concentration (Cmax) was 19.54 µg/ml was achieved at a maximum time (Tmax) of 2.42 h. The intramuscular bioavailability of cefotaxime in normal chickens was 81.92 %.  Intramuscular injection cefotaxime twice daily for five consecutive days in normal and Staphylococcus aureus infected chickens revealed a lower significant serum cefotaxime concentration after the first, third, fifth, seventh, ninth doses in Staphylococcus aureus infected chickens compared with normal chickens. Cefotaxime showed accumulative behavior in blood of chickens. After repeated intramuscular injection of 25 mg cefotaxime/kg b.wt every 12 h, cefotaxime was assayed in liver, kidney, lung, heart, breast muscle, thigh muscle and skin after 24, 48, 72, 96, 120 and 144 h post last dose. Drug concentrations in liver, kidney and lung were (23.17 ± 0.614) (15.51 ± 0.31), (16.69 ± 0.405) (10.94 ± 0.04) and (14.04 ± 0.52) (7.92 ± 0.395)   µg/g in normal and Staphylococcus aureus infected chickens respectively 24 hours after the stoppage of drug medication. Cefotaxime was completely cleared from tissues at 144 and 120 hours after the stoppage of drug dosage in normal and Staphylococcus aureus infected chickens. Results of this study indicated that cefotaxime was useful for treatment of Staphylococcus aureus infections in chickens.