The present work was carried out to test the impact of oral probiotics on the pharmacokinetics of difloxacin (IV and oral; 10mg/kg b.wt) and its tissue residues in broiler chickens. Blood samples were taken over 24 h of difloxacin administration for the pharmacokinetic study. For testing difloxacin residues, the drug was administered orally at the same dose for 5 successive days and the edible tissues (muscle, liver, kidney and gizzard) were collected from slaughtered birds after 1, 3, 5 and 7 days of the last dose. The drug was estimated by using high-performance liquid chromatography (HPLC). The two-compartment open model was applied to describe the plasma concentration-time data of difloxacin. Analysis of the data following intravenous (IV) administration revealed a significantly higher plasma concentration of difloxacin (0.16 +/- 0.0 vs 0.13 +/- 0.0 mu g/ml at 24 h post injection; P<0.05) and a significantly prolonged half-life (4.09 +/- 0.03 vs 3.75 +/- 0.02 h) in probiotic-pretreated chickens as compared to non-treated one. The absorption half-life (t(0.5ab)) of difloxacin was 1.34 +/- 0.03 and 1.43 +/- 0.04 h (P<0.05) and the calculated oral bioavailability (F) was 72.82 +/- 5.35% and 64.56 +/- 5.29% in chickens with and without probiotic pretreatment, respectively. The elimination half-life of difloxacin was more prolonged (P<0.05) in probiotic pretreated chickens. The residues levels in muscle, liver and kidney were lower in probiotic-pretreated chickens. Twenty-four hours after the last oral dose, the tissue residues of difloxacin were lower than the recommended MRLs in chicken. In conclusion, the use of probiotic modulate pharmacokinetics and tissue residue of difloxacin and increase its bioavailability. (C) 2020 PVJ. All rights reserved