Background　and　Aims.　Osteosarcoma　is　one　of　the　most　pernicious　primary　bone　tumor　characterized　by　high　malignancy　and　metastasis,　however　its　pathogenesis　remain　largely　unknown.　Our　previous　study　showed　elevated　expression　of　adrenomedullin　(ADM)　is　correlated　with　prognosis　and　disease　severity　in　osteosarcoma　patients.　In　this　research,　we　continue　to　study　the　mechanisms　of　ADM-induced　osteosarcoma　cells　proliferation　in　vitro　and　in　vivo　osteosarcoma　models.　Methods.　The　Radioimmunoassay　was　used　to　test　the　correlations　of　ADM　and　vascular　endothelial　growth　factor　(VEGF)　expressions　in　plasma　of　osteosarcoma　patients.　The　MTT　and　flow　cytometry　analysis　were　accepted　to　monitor　the　proliferation　of　osteosarcoma　cells,　meanwhile　the　ADM　and　VEGF　expression　were　detected　by　real-time　PCR　and　western　blot.　Moreover,　the　relationship　among　ADM　and　VEGF　expression　was　also　assessed　in　the　osteosarcoma　nude　mice　models.　Results.　In　this　study,　a　significant　correlation　was　found　between　ADM　and　VEGF　expression　in　the　plasma　of　osteosarcoma　patients.　As　important　stimuli　in　osteosarcoma　proliferation,　hypoxia　could　stimulate　ADM　and　VEGF　expression　in　MG-63　cells.　The　expressions　of　ADM　and　VEGF　increased　with　the　duration　of　hypoxia,　which　also　identify　the　positive　correlations　between　the　expression　of　ADM　and　VEGF.　The　proliferation　of　MG-63　cells　decreased　when　ADM　was　inhibited.　And　the　proliferation　increased　when　adding　exogenous　ADM,　while　VEGF　inhibition　attenuated　this　effect.　Furthermore,　ADM　reduction　also　inhibited　VEGF,　CD31　expression　and　tumor　cells　growth　in　osteosarcoma　nude　mice　models.　Conclusion.　These　results　suggested　inhibition　of　osteosarcoma　cells　proliferation　might　be　influenced　by　ADM　through　VEGF　pathway,　which　implied　ADM-VEGF　signal　was　a　potential　target　for　impeding　the　proliferation　of　malignant　cells　in　osteosarcoma.　(C)　2019　IMSS.　Published　by　Elsevier　Inc.