Although　the　CXCL12-CXCR4/CXCR7　chemokine　axis　is　demonstrated　to　play　an　integral　role　in　tumor　progression,　the　controversy　exists　and　the　role　of　CXCL12-CXCR4/CXCR7　signaling　axis　in　epithelial-mesenchymal　transition　(EMT)　of　human　ovarian　cancer　has　not　been　explored.　Here,　we　showed　that　in　ovarian　cancer　CXCL12　induced　EMT　phenotypes　including　the　spindle-like　cell　morphology,　podia　and　stress　fiber　formation,　a　decrease　in　E-cadherin　expression,　and　increases　in　mesenchymal　N-cadherin　and　vimentin　expressions.　These　effects　of　CXCL12　could　be　antagonized　by　the　CXCR4　antagonist　AMD3100,　but　not　by　the　anti-CXCR7　antibody.　The　expressions　of　the　EMT　markers　were　significantly　down-regulated　by　the　CXCR4　siRNA,　and　up-regulated　by　the　pcDNA3.1/CXCR4　plasmid,　whereas　not　affected　by　the　CXCR7　siRNA.　Furthermore,　intraperitoneal　administration　of　AMD3100　inhibited　tumor　dissemination　and　growth　in　the　nude　mice　inoculated　with　ovarian　IGROV-1　cells　with　a　concomitant　reduction　in　EMT　marker　expressions.　Collectively,　these　data　suggest　that　CXCR4,　rather　than　CXCR7,　plays　a　key　role　in　CXCL12-activated　EMT　phenotypes,　and　targeting　the　CXCL12-CXCR4　chemokine　axis　represents　a　potential　therapeutic　strategy　to　prevent　ovarian　cancer　progression.