Abstract: The systemic bioavailability and lung tissue distribution of valnemulin were investigated in swine. About 65 pigs received 10 mg kg-1 body weight of valnemulin by either intravenous (i.v.) or oral (p.o.) route in two studies: study A (10 pigs, i.v. or p.o.) and study B (55 pigs, p.o.). The plasma and lung tissue concentration of the drug were determined by a validated HPLC-MS/MS method. Plasma concentration-time data after i.v. administration (10 mg kg-1 b.w.) were best described by a two-compartment open model. The pharmacokinetic parameters were elimination rate (ke) 0.95±0.17 h-1, the maximum concentrations 4.63±0.66 μg mL-1, area under the plasma concentration-time curve (AUCinf) 5.30±0.37 (h*μg) mL-1. On the other hand, A one-compartment model with a 1st order absorption rate was best fitted to the plasma concentration-time curve of valnemulin after oral administration (10 mg kg-1 b.w.) and the absorption rate (ka) was 0.34±0.03 h-1, the elimination rate (ke) was 1.05±0.19 h-1, the maximum concentration was 0.59±0.08 μg mL-1 at 1.98±0.21 h (tmax), the mean p.o. bioavailability (F) was 57.43%. Following p.o. administration, a mean valnemulin concentration of 0.14 μg g-1 was detected in lung tissue at 36 h postdosing. The lung AUCinf (410.16 h*μg g-1) was 77.39 times higher than the corresponding plasma AUCinf (5.30 h*μg g-1). The apparent elimination half-time for valnemulin in lung was 3.57 h. The advisable bioavailability and extensive distribution to lung tissue following a single dose of valnemulin may be desirable pharmacokinetic attributes for an antimicrobial drug used for the treatment and prevention of respiratory disease in swine.