Dietary factors are involved in the regulation and prevention of type 2 diabetes mellitus. We have shown that cinnamon improves glucose and lipids of people with type 2 diabetes and that a water-soluble cinnamon extract and HPLC-purified cinnamon polyphenols (CP) display insulin-like activity. The objective of this study was to investigate the biochemical basis for the insulin-like effects of cinnamon. Immunoblotting procedure was employed to analyze three of the proteins, insulin receptor β, glucose transporter 4, and the anti-inflammatory protein tristetraprolin (TTP) involved in insulin signal transduction pathway using mouse 3T3-L1 adipocytes. The results show that both insulin and CP increased the levels of the three proteins. Recombinant TTP was phosphorylated in vitro by glycogen synthase kinase 3β and protein kinases A, Bα, and Cμ. These results suggest that cinnamon polyphenols, like insulin, increase the amount of the three critically important proteins involved in insulin signaling, glucose transport and inflammatory response. A model of actions was proposed to link CP and TTP in insulin signal transduction pathway. This study provides new biochemical evidence for the beneficial effects of cinnamon polyphenols in potentiating insulin action and suggests anti-inflammatory properties of cinnamon polyphenols (Supported in part by USDA-ARS, NIH-NIEHS, and PhytoMedical Technologies)