Rutin　is　a　flavonoid　that　exists　in　plants　and　in　commonly　consumed　foods.　In　recent　years,　rutin　has　been　demonstrated　to　have　anti-thrombotic　efficacy　through　its　inhibition　of　protein　disulfide　isomerase.　However,　the　low　aqueous　solubility　and　high　dose　limit　the　therapeutic　applications　of　rutin.　In　this　study,　we　found　that　the　chelation　of　zinc　ions　increased　rutin　aqueous　solubility　by　4-fold.　More　importantly,　the　thus-formed　rutin:Zn　complex　inhibited　PDI　activity　more　potently　than　rutin　itself.　In　a　murine　model　with　electric　current-induced　arterial　thrombosis,　the　rutin:Zn　complex　slowed　mouse　arterial　occlusion　compared　to　rutin　without　increasing　bleeding　risk.　Thus,　the　zinc　chelation　not　only　improved　rutin　aqueous　solubility　but　achieved　stronger　inhibition　of　PDI.　Furthermore,　zinc　chelation　of　a　selected　list　of　flavonoids　containing　the　adjacent　keto　and　phenoxy　groups　also　increased　their　inhibition　of　PDI.　Hence,　our　study　provides　a　strategy　to　promote　flavonoids＇　anti-thrombotic　properties.