Background-Cardiac　fibrosis　is　a　core　pathological　process　associated　with　heart　failure.　The　recruitment　and　differentiation　of　primitive　fibroblast　precursor　cells　of　bone　marrow　origin　play　a　critical　role　in　pathological　interstitial　cardiac　fibrosis.　The　K(Ca)3.1　channels　are　expressed　in　both　ventricular　fibroblasts　and　circulating　mononuclear　cells　in　rats　and　are　upregulated　by　angiotensin　II.　We　hypothesized　that　K(Ca)3.1　channels　mediate　the　inflammatory　microenvironment　in　the　heart,　promoting　the　infiltrated　bone　marrow-derived　circulating　mononuclear　cells　to　differentiate　into　myofibroblasts,　leading　to　myocardial　fibrosis.　Methods　and　Results-We　established　a　cardiac　fibrosis　model　in　rats　by　infusing　angiotensin　II　to　evaluate　the　impact　of　the　specific　K(Ca)3.1　channel　blocker　TRAM-34　on　cardiac　fibrosis.　At　the　same　time,　mouse　CD4(+)　T　cells　and　rat　circulating　mononuclear　cells　were　separated　to　investigate　the　underlying　mechanism　of　the　TRAM-34　anti-cardiac　fibrosis　effect.　TRAM-34　significantly　attenuated　cardiac　fibrosis　and　the　inflammatory　reaction　and　reduced　the　number　of　fibroblast　precursor　cells　and　myofibroblasts.　Inhibition　of　K(Ca)3.1　channels　suppressed　angiotensin　II-stimulated　expression　and　secretion　of　interleukin-4　and　interleukin-13　in　CD4(+)　T　cells　and　interleukin-4-　or　interleukin-13-induced　differentiation　of　monocytes　into　fibrocytes.　Conclusions-K(Ca)3.1　channels　facilitate　myocardial　inflammation　and　the　differentiation　of　bone　marrow-derived　monocytes　into　myofibroblasts　in　cardiac　fibrosis　caused　by　angiotensin　II　infusion.