The　present　work　proposed　a　novel　ECL　protocol　to　probe　the　interactions　between　mimic　enzymes　and　small　biological　molecules.　Iron(II)　phthalocyanine　(FePc)　and　two　imidazoles　(imidazole　and　histidine)　were　chosen　as　model　molecules　of　mimic　enzyme　and　small　biological　molecules,　respectively.　The　interactions　between　FePc　and　the　imidazoles　were　probed　by　a　sensitive　luminol-O2　ECL　system.　Before　complexing　with　the　imidazoles,　FePc　can　inhibit　luminol-O2　ECL　due　to　its　electrocatalysis　towards　O2,　however,　after　complexing　with　the　imidazoles,　FePc　decreases　the　electrocatalysis,　leading　to　the　observation　of　an　enhanced　luminol-O2　ECL.　Additionally,　the　proposed　protocol　enables　detection　limits　of　1.0　×　10-8　mol　L-1　and　1.0　×　10-7　mol　L-1　to　be　achieved,　respectively,　for　imidazole　and　histidine　under　the　physiological　pH　condition　(pH　7.4).　©　2008　Elsevier　B.V.　All　rights　reserved.