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This study was designed to investigate the efficacy of intratracheal (IT) instillation of meropenem using PFC liquid as a vehicle in a piglet model of acute lung injury (ALI). Eighteen piglets were injured with lung lavages to induce ALI, and randomly assigned to intravenous (IV) infusion or IT instillation groups, the latter using either PFC or normal saline (NS) as a delivery vehicle for meropenem. Blood samples were obtained at 0, 15, 30, and 60\u2009min, and then hourly for 6\u2009hr. Sera and extracts of lung tissues were assayed for meropenem content using high\u2010performance liquid chromatography. We found that the IV group had significantly higher serum concentrations of meropenem during the first hour after dosing (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). There was no significant difference between IT\u2010PFC and IT\u2010NS groups regarding changes in serum meropenem concentrations during the experimental period. Meropenem content in lung tissue was highest in the IT\u2010PFC group, lower in the IT\u2010NS group, and undetectable in the IV group (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). The IT\u2010NS group had the highest peak inspiratory pressure (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05), but there were no significant differences in other cardiopulmonary parameters among the three groups studied. In conclusion, meropenem can be safely administered to injured lungs by IT instillation in a meropenem\/PFC suspension. Using PFC liquid as an IT vehicle to carry meropenem provides better pulmonary drug depositions than IV injection or IT instillation with NS in ALI. 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