The role of 17-beta-estradiol and progesterone on glucose homeostasis was examined in pregnant and non pregnant rats with or without food restriction (50%). Blood glucose and insulin levels were significantly decreased in food restricted pregnant (PM) compared with control pregnant (PC) and in food restricted non pregnant (M) compared with non pregnant control (C). The plasmatic level of progesterone was similar in PC and PM, while the plasmatic level of 17-beta-estradiol was significantly decreased in PM compared with PC at 15 and 20 days. In spite of food restriction, the changes in the insulin/glucose ratio throughout gestation were similar in PC and PM. A positive and significant relation between 17-beta-estradiol and the level of insulin at day 5 of gestation, and a negative and significant relation between the level of 17-beta-estradiol and level of insulin at day 15 of gestation were found in PC. A negative and significant relation between the levels of progesterone and the levels of insulin at day 5 of gestation, at day 10 this relation is positive and significative, and at day 15 a positive and significant relation exists between levels of 17-beta-estradiol and levels of insulin were found in PM. These results suggest that 17-beta-estradiol acts directly on beta-cells to control insulin secretion. Food restriction does not alter the changes in the sensitivity of tissues to the insulin action, and does modify the action of 17-beta-estradiol and progesterone on beta-cell.