The pharmacokinetic profile of ceftiofur sodium, a third generation cephalosporin, was studied in both Friesian and buffalo calves following a single intravenous and intramuscular administration of 2.2 mg kg-1 b.wt. in a cross over study with 15-day wash out period. After i.v administration the serum concentration-time curve of ceftiofur sodium was best fitted using two-compartments open model, with distribution half-lives (t½(()) of 0.384 and 0.176 h., elimination half-lives (t½(0)) of 5.047 and 1.607 h., mean residence time (MRT) of 6.926 and 2.072 h., volumes of distribution at steady-state (Vdss) of 0.206 and 0.134 L kg-1 and total body clearance (ClB) of 0.029 and 0.065 L kg-1 h-1 in Friesian and buffalo calves,  respectively. Following intramuscular administration, the drug absorbed with half-lives of absorption (t½(ab)) of 1.010 and 0.217 h., maximum serum concentrations (Cmax) of 5.539 and 9.663
g ml-1 which attained after (tmax) of 3.147 and 0.825 h. and the drug was eliminated with half-lives (t½(el)) of 5.239 and 1.750 h. in Friesian and buffalo calves, respectively. The systemic intramuscular bioavailabilities were 89.82 and 99.7 %, while the in-vitro serum proteinbinding tendencies were 39.68 and 14.44 % in Friesian and buffalo calves, respectively