Glucocorticoids are known to impair oral glucose tolerance and to induce insulin resistance. It has also been reported that glucocorticoids stimulate absorption of glucose, water, and electrolytes from the gut. The aim of the present study was to determine if dexamethasone treatment increased the rate of appearance in plasma of gut-derived glucose. Glucose turnover was measured following an oral glucose load in chronically catheterized, nonstressed rats treated for 96 hours with either normal saline (n = 14) or dexamethasone (5 micrograms twice daily intravenously [IV] (n = 10). Dexamethasone-treated rats had mild glucose intolerance and higher insulin levels than control rats. Total glucose turnover was increased at all time points following the glucose drink in the dexamethasone-treated rats, as was the rate of appearance of gut-derived glucose (154 +/- 25 v 321 +/- 62 mg/45 min; P = .018). It is concluded that in rats, dexamethasone treatment increases the rate of appearance in plasma of orally administered glucose.