Ets-1,　the　prototypical　member　of　the　family　of　Ets　transcription　factors,　has　been　shown　to　participate　in　tissue　fibrotic　remodeling.　However,　its　role　in　cardiac　fibrosis　has　not　been　established.　The　aim　of　this　study　was　to　investigate　the　role　of　Ets-1　in　profibrotic　actions　of　angiotensin　II　(Ang　II)　in　cardiac　fibroblasts　(CFs)　and　in　the　in　vivo　heart.　In　growth-arrested　CFs,　Ang　II　induced　Ets-1　expression　in　a　time-　and　concentration-dependent　manner.　Pretreatment　with　Ang　II　type　1　receptor　blocker　losartan,　protein　kinase　C　inhibitor　bisindolylmaleimide　I,　extracellular　signal-regulated　kinase　(ERK)　inhibitor　PD98059,　or　c-Jun　NH(2)-terminal　kinase　(JNK)　inhibitor　SP600125　partly　inhibited　this　induction　accompanied　with　impaired　cell　proliferation　and　production　of　plasminogen　activator　inhibitor-1　(PAI-1)　and　connective　tissue　growth　factor　(CTGF)　protein,　the　two　downstream　targets　of　Ets-1.　Knockdown　of　Ets-1　by　siRNA　significantly　inhibited　the　inductive　effects　of　Ang　II　on　cell　proliferation　and　expression　of　CTGF　and　PAI-1.　Moreover,　the　levels　of　Ets-1,　PAI-1　and　CTGF　protein　were　simultaneously　upregulated　in　left　ventricle　of　Ang　II-infused　rats　in　parallel　with　an　increase　in　the　activation　of　ERK　and　JNK.　Our　data　suggest　that　Ets-1　may　mediate　Ang　II-induced　cardiac　fibrotic　effects.