Blast　lung　injury　is　associated　with　high　morbidity　and　mortality.　Vaporized　perfluorocarbon　(PFC)　inhalation　has　been　reported　to　attenuate　acute　respiratory　distress　syndrome　in　humans　and　animal　models.　However,　the　effect　of　vaporized　PFC　on　blast　lung　injury　is　still　unknown.　In　this　study,　we　investigated　the　protective　effects　and　potential　underlying　mechanisms　of　action　of　vaporized　PFC　on　blast　lung　injury　in　a　canine　model.　This　was　a　prospective,　controlled,　animal　study　in　adult　male　hybrid　dogs　randomized　to　sham,　blast　(B),　blast　plus　mechanical　ventilation　(B　+　M),　and　blast　plus　PFC　(B　+　P)　groups.　All　groups　except　for　the　sham　were　exposed　to　blast　wave.　The　B　+　P　group　was　treated　with　vaporized　PFC　for　1.5　h　followed　by　5.5　h　mechanical　ventilation.　B　+　M　group　received　7.5　h　mechanical　ventilation　and　B　group　was　observed　for　7.5　h.　Blast　lung　injury　was　induced　using　a　shock　tube.　Blood　gas,　inflammatory　cytokines,　and　oxidative　stress　were　measured.　Expression　of　nuclear　factor　(NF)-kappa　B　activation,　mitogen-activated　protein　kinase　(MAPK)　and　nuclear　factor,　erythroid　2　like　2　(Nrf2)　were　measured　using　western　blot.　Lung　injury　observed　after　blast　exposure　was　marked　by　increased　histopathological　scores,　ratio　of　lung　wet　to　dry　weight.　PFC　treatment　attenuated　blast　lung　injury　as　indicated　by　histopathological　scores　and　ratio　of　lung　wet　to　dry　weight.　PFC　treatment　down-regulated　interleukin　(IL)-6,　tumor　necrosis　factor　(TNF)-alpha,　and　malondialdehyde　(MDA),　and　upregulated　superoxide　dismutase　(SOD)　activity.　PFC　also　suppressed　expression　of　MAPK/NF-kappa　B　and　Nrf2　protein　levels.　Our　results　suggest　that　PFC　attenuated　blast-induced　acute　lung　injury　by　inhibiting　MAPK/NF-kappa　B　activation　and　inducing　Nrf2　expression　in　dogs.