This work continues our studies of the mechanisms of transformation of the initial gastroprotective action of glucocorticoid hormones into a proulcerogenic action. Experiments on rats tested the suggestion that the development of insulin resistance after prolonged exposure to glucocorticoid hormones may be one of the mechanisms of this transformation. This was addressed by studying the effects of dexamethasone, corticosterone, and hydrocortisone on insulin sensitivity at different time points after single doses of pharmacological size. Insulin sensitivity was evaluated in terms of the decrease in the blood glucose level 1.5 h after administration of insulin (2 IU/kg, i.p.). Decreases in glucose levels were expressed as percentages of baseline (pre-insulin) glucose levels. The results indicated that at those time points at which these hormone had previously been found to have gastroprotective actions, insulin sensitivity remained unaltered from that in control animals. Administration of dexamethasone and hydrocortisone after prolonged exposure led to decreases in insulin sensitivity at those time points at which their proulcerogenic effects had been seen. Increases in the duration of exposure to corticosterone did not produce any changes in insulin sensitivity or transformation of its gastroprotective effect into a proulcerogenic action. These data support the suggestion that the development of insulin resistance after prolonged exposure to glucocorticoid hormones can be regarded as one of the mechanisms of the transformation of their gastroprotective effects into proulcerogenic actions.