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Background Retinol binding protein 4 (RBP4),as an adipocyte secreted cytokine,was recently found to be inversely correlated with expression of glucose transporter 4 (GLUT4) in insulin resistance (IR) state and to have an intimate relationship with IR and type 2 diabetes mellitus (T2DM).The present study aimed to evaluate the anti-diabetic efficacy of cinnamaldehyde (tin),berberine (Bet),and metformin (Met) as well as their impacts on the RBP4-GLUT4 system.Methods Rat models of T2DM were established by combination of intraperitoneal injection of low-dose streptozotocin and high fat diet induction.Rats were divided into five groups:the control group,the diabetes group,the diabetes+Ber group,the diabetes+Cin group,and the diabetes+Met group.West blotting was used to detect the serum or tissue RBP4 and GLUT4 protein levels.Results After treatment for four weeks,both Cin and Ber displayed significant hypolipidemic,hypoglycemic,and insulin sensitizing functions (P<0.01) compared with the control group.Their effects on lowering fasting plasma glucose (FPG),low density lipoprotein-cholesterol (LDL-C) and homeostasis model assessment of insulin resistance (HOMA-IR) seem even better than that of Met.Cin and Bet markedly lowered serum RBP4 levels and up-regulated the expression of tissue GLUT4 protein,and Cin seemed more notable in affecting these two proteins.Conclusions Both Cin and Ber display an exciting anti-diabetic efficacy in this study and may be of great value for the treatment of type 2 diabetes.Their mechanisms involve the RBP4-GLUT4 system,during which the serum RBP4 levels are lowered and the expression of tissue GLUT4 protein is up-regulated.