Several studies revealed that the trace element selenium and the long-acting GLP-1 analogue, exendin-4, exert antidiabetic effects by unknown mechanisms. In this study, we investigated the effects of treatment of diabetic rats with selenium, combined insulin and selenium or combined selenium and exendin-4 for 6 days on blood glucose level, body weight and steady-state mRNA levels of insulin receptor (IR), glucagon-like peptide 1 receptor (GLP-1R) and some of their signal transducers as well as glucose transporters 2 and 4 (GLUT2 and GLUT4) in the liver. Diabetes was induced by single intraperitoneal injection of 65 mg of streptozotocin/kg body weight, selenium was administered as 5 ppm sodium selenite in drinking water, insulin was injected intravenously twice daily at a dose of 4 U/Kg body weight and intraperitoneal injections of 0.03 μg/Kg body weight twice daily were used for administration of exendin-4. Induction of diabetes resulted in significant hyperglycemia, body weight loss and decrease in hepatic steady-state mRNA levels of GLP-1R, IR and the key downstream signal transducers IRS-1, PI3K, PDK1, PKC and AKT as well as in GLUT2 and GLUT4. Selenium treatment for 6 days resulted in significant increase in hepatic steady-state mRNA levels of IR with significant body weight gain as compared to non-treated diabetic rats. Treatment of diabetic rats for 6 days with a combination of insulin and selenium resulted in significant increase in hepatic steadystate mRNA levels of IR, PI3K, PDK1and AKT as compared to their levels in the diabetic rats that received no treatment. Interestingly, the combined treatment of diabetic rats with selenium and exendin-4 resulted in increased hepatic steady-state mRNA levels of GLP-1R, IR, IRS-1, PI3K, PDK1, PKC and AKT, GLUT2 and GLUT4 back to normal range, blood glucose level and body weight close to the normal as compared to the control rats. Therefore, the antidiabetic effects of selenium and exendin-4 may result from their effects on the steady-state mRNA levels of GLP-1R, IR, IRS-1, PI3K, PDK1, PKC, AKT, GLUT2 and GLUT4 in the liver.