Hemopexin,　a　high　affinity　heme-binding　protein　is　widely　involved　in　variety　physiological　and　pathological　processes.　It　is　an　important　acute　phase　response　protein,　and　is　important　in　regulating　the　inflammatory　response.　In　this　study,　the　open　reading　frame　of　Nile　tilapia　hemopexin　(OnHpx)　gene　was　amplified.　The　expression　pattern　of　OnHpx　in　natural　and　bacterial　challenged　tilapia　tissues　were　analyzed　through　RT-qPCR.　The　results　indicated　the　OnHpx　was　most　abundant　in　liver,　and　increased　significantly　in　liver,　spleen,　head　kidney　and　peripheral　blood　after　bacterial　challenge.　Furthermore,　the　OnHpx　mRNA　was　also　significantly　up　regulated　in　monocytes/macrophages　and　hepatocytes　under　the　stimulation　of　S.　agalactiae　or　A.　hydrophila.　In　addition,　the　recombinant　OnHpx　protein　could　effectively　reduce　the　bacteria　proliferation　and　alleviate　the　inflammatory　reaction　caused　by　bacteria.　Moreover,　the　(r)OnHpx　also　regulated　the　respiratory　burst　of　monocytes/macrophages　and　played　an　important　role　in　the　antioxidant　process.　To　our　knowledge,　these　results　provide　the　first　evidence　on　the　antibacterial　and　anti-inflammatory　response　mechanism　of　Hpx　in　early　vertebrates.　This　brings　new　insights　about　the　understanding　of　the　evolutionary　origins　and　ancient　roles　of　the　Hpx　in　the　innate　immune　defense.