Diabetes mellitus is attacking over 170 million people worldwide, with more than 90% of the patients having type 2 diabetes. A recent study has shown that exendin-4 and selenium exert an antidiabetic effect. The present study investigated the effects of treatment of diabetic rats with selenium, insulin, or a combination of selenium and insulin or selenium and exendin-4 on the steady-state mRNA level of several selenoprotein genes (glutathione peroxidase 1 (Gpx1), selenoprotein P (SeP), selenophosphate synthetase 2 (SPS2), thioredoxin reductase (TR1)) thioredoxin (Trx1) and thioredoxin interacting ptotein (Txnip). Diabetes was induced in Sprague Dawley rats using 65 mg STZ/kg body weight. Six groups of male rats were used: normal rats, diabetic rats, diabetic rats treated with insulin, diabetic rats treated with 5ppm selenium as sodium selenite in drinking water, diabetic rats treated with a combination of selenium and insulin, diabetic rats treated with a combination of selenium and exendin-4. After 6 days of treatment all rats were sacrificed. Total RNA was extracted from all liver samples, then cDNA was synthesized from mRNA, and Real-time PCR assays were used to determine the steady-state mRNA level of all these genes. The results of this study showed that the steady-state mRNA levels of Txnip, SPS2, TR1, SeP in the liver were significantly increased in diabetic rats as compared to control rats, while Gpx1 steady state level decreased in the liver of diabetic rats. Insulin treatment of diabetic rats decreased the steady-state mRNA level of SeP, TR1, SPS2, Trx1 and increased Txnip steady-state. Selenium treatment of diabetic rats increased the steady-state mRNA levels of SeP and Gpx1 and decreased the steady-state mRNA levels of Txnip, Trx1, and TR1. The combination of selenium and insulin treatment decreased the steady-state mRNA levels of all selenoproteins, Txnip and Trx1 with the exception of Gpx1. In addition, the combination of selenium and exendin-4 restored the normal levels of steady-state mRNA of SeP, TR1, and SPS2 as compared to the control rats. Therefore, the effects of selenium and exendin-4 on diabetes may result from influencing the steady-state mRNA levels of these selenoproteins, Trx1 and Txnip.