Phenotypic　switching　of　vascular　smooth　muscle　cells　(VSMCs)　plays　a　critical　role　in　atherosclerosis,　vascular　restenosis,　and　hypertension.　Choline　exerts　cardioprotective　effects;　however,　little　is　known　about　its　effects　on　VSMC　phenotypic　switching　and　vascular　remodeling.　Here,　we　investigated　whether　choline　modulates　VSMC　phenotypic　changes　and　explored　the　underlying　mechanisms.　Approach　and　Results:　In　cultured　VSMCs,　choline　promoted　Nrf2　(nuclear　factor　erythroid　2-related　factor　2)　nuclear　translocation,　inducing　the　expression　of　HO-1　(heme　oxygenase-1)　and　NQO-1　(NAD[P]H　quinone　oxidoreductase-1).　Consequently,　choline　ameliorated　Ang　II　(angiotensin　II)-induced　increases　in　NOX　(NAD[P]H　oxidase)　expression　and　the　mitochondrial　reactive　oxygen　species　level,　thereby　attenuating　Ang　II-induced　VSMC　phenotypic　switching,　proliferation,　and　migration,　presumably　via　M3AChRs　(type　3　muscarinic　acetylcholine　receptors).　Downregulation　of　M3AChR　or　Nrf2　diminished　choline-mediated　upregulation　of　Nrf2,　HO-1,　and　NQO-1　expression,　as　well　as　inhibition　of　VSMC　phenotypic　transformation,　suggesting　that　M3AChR　and　Nrf2　activation　are　responsible　for　the　protective　effects　of　choline.　Moreover,　activation　of　the　Nrf2　pathway　by　sulforaphane　suppressed　Ang　II-induced　VSMC　phenotypic　switching　and　proliferation,　indicating　that　Nrf2　is　a　key　regulator　of　VSMC　phenotypic　switching　and　vascular　homeostasis.　In　a　rat　model　of　abdominal　aortic　constriction　in　vivo,　choline　attenuated　VSMC　phenotypic　transformation　and　vascular　remodeling　in　a　manner　related　to　activation　of　the　Nrf2　pathway.These　results　reveal　that　choline　impedes　VSMC　phenotypic　switching,　proliferation,　migration,　and　vascular　remodeling　by　activating　M3AChR　and　Nrf2-antioxidant　signaling　and　suggest　a　novel　role　for　Nrf2　in　VSMC　phenotypic　modulation.