Lung　is　one　of　the　most　common　sites　for　bladder　cancer　to　metastasize.　Although　the　involvement　of　the　epithelial-to-mesenchymal　transition　(EMT)　in　bladder　cancer　progression　has　been　established,　the　mechanism　of　EMT　induction　remains　unclear.　In　order　to　investigate　this,　T24-parental　(P)　and　T24-lung　(L)　bladder　cancer　cells　were　obtained　from　primary　tumors　and　lung　metastatic　sites　of　an　animal　model　with　orthotopic　spontaneous　metastatic　bladder　cancer,　according　to　a　protocol　previously　described.　Compared　with　T24-P　cells,　mesenchymal-like　T24-L　cells　exhibited　an　increased　ability　in　tumor　invasion　and　metastasis,　as　well　as　an　increased　expression　of　hypoxia-inducible　factor　(HIF)-1　alpha,　zinc　finger　E-box-binding　homeobox　1　(ZEB1),　vimentin　and　N-cadherin　and　lower　level　of　cytokeratin　18　were　observed.　Mechanistically,　it　was　identified　that　HIF-1　alpha　increases　ZEB1　expression　and　subsequently　regulates　the　expression　of　EMT-related　genes　in　both　HIF-1　alpha　knocking　down　by　siRNA　and　gain-in　HIF-1　alpha　by　hypoxia　culture　cell　models.　In　addition,　the　expression　of　HIF-1　alpha　and　ZEB1　in　bladder　cancer　tissues　were　increased　compared　with　normal　bladder　epithelial　tissues,　as　well　as　significantly　increased　in　the　high-grade,　invasive　and　metastatic　bladder　cancer　tissues　compared　with　low-grade,　superficial　and　non-metastatic　bladder　cancer　tissues　by　using　immune-histochemical　staining　assay.　Notably,　the　protein　level　of　HIF-1　alpha　was　positively　associated　with　that　of　ZEB1　in　bladder　cancer　tissues.　Results　from　the　present　study　indicate　that　HIF-1　alpha　promotes　ZEB1　expression　and　EMT　in　the　T24-L　human　bladder　cancer　lung　metastasis　animal　model,　suggesting　that　HIF-1　alpha　serves　an　important　function　in　the　metastasis　of　bladder　cancer,　and　HIF-1　alpha　and　ZEB1　may　be　potential　targets　for　inhibiting　bladder　metastasis　in　the　future.