In this present study, we found that short term intervention of dietary capsaicin, a highly selective agonist for TRPV1, increased insulin signaling pathway in hippocampus, which leads to inhibition of GSK-3β, prevention of hyperphosphorylation of tau protein and improved glucose metabolism and insulin resistance without affecting body weight in a rat model of type 2 diabetes. This evidence concerns the gene GSK3B and type 2 diabetes mellitus.