The objective of the present study was to investigate the effects of oral selenate application in comparison to selenium deficiency and selenite treatment on the development of the diabetic status (glucose tolerance, insulin resistance and activities of glycolytic and gluconeogenic marker enzymes) in dbdb mice, representing a type II diabetic animal model. Therefore 21 adult male dbdb mice were assigned to 3 experimental groups of 7 animals each and put on a selenium deficient diet (< 0.03 mg/kg diet) based on torula yeast. Group 0Se was kept on selenium deficiency for 10 weeks while the mice of the groups SeIV and SeVI were supplemented daily with 15% of their individual LD(50) of sodium selenite or sodium selenate in addition to the diet. After 10 weeks a distinct melioration of the diabetic status indicated by a corrected glucose tolerance and a lowered insulin resistance was measured in selenate treated mice (group SeVI) in comparison to their selenium deficient and selenite treated companions and to their initial status. Activities of the glycolytic marker enzymes hexokinase, phosphofructokinase and pyruvate kinase were increased 1.7 to 3-fold in liver and/or adipose tissue by selenate treatment as compared to mice on selenium deficiency and mice with selenite administration. In contrast selenate treatment (SeVI) repressed the activity of liver pyruvate carboxylase the first enzyme in gluconeogenesis by about 33% in comparison to the selenium deficient (0Se) and selenite treated mice (SeIV). However the current study revealed an insulinomimetic role for selenate (selenium VI) also in type II diabetic animals due to a melioration of insulin resistance. In contrast selenium deficiency and especially selenite (selenium IV) impaired the diabetic status of dbdb mice, demonstrating the need for investigations on the insulinomimetic action of selenium due to the metabolism of different selenium compounds.