In light of Txnip in pathological process in T2DM and the central role of Chrebp in the regulation of Txnip, here we investigated whether S-Equol affects insulin secretion and influences the Chrebp/Txnip signaling both in vivo and in vitro, which would support new evidences to demonstrate the effects and mechanisms of S-Equol on diabetes. This evidence concerns the gene INS and diabetes mellitus.