The association of obesity with type 2 diabetes mellitus has been recognized for years. In type 2 diabetes, there is a possibility that an important part of the impaired insulin secretion is due to the gastric inhibitory polypeptide (GIP) hormone. This study investigated changes that occur in the pancreatic GIP receptors' (GIP-Rs) expression and in GIP secretion in obese and type 2 diabetic rats and its relation to plasma glucose and insulin levels during oral glucose tolerance test (OGTT) compared to control rats. During the first 20 min of the OGTT, both the obese and the diabetic rats had a significant increase in the glucose excursion and a significant decrease in early-insulin secretion compared to the control group, with more prominent changes in the diabetic group. The obese rats had a significant increase in fasting GIP level and in the incremental change of GIP from 0 to 20 min (GIP Delta 0-20: 60.1 + or - 6.66 pmol/l) compared to that of the control (33.96 + or - 4.69 pmol/l) and the diabetic (29.34 + or - 2.62 pmol/l) group, which were not significantly different from each other. However, there was a significant decrease in GIP-Rs expression in both the obese (88.07 + or - 10.36 microg/ml) and diabetic (87.51 + or - 4.72 microg/ml) groups compared to the control group (120.35 + or - 8.06 microg/ml). During the second hour of the OGTT, plasma GIP was decreasing in all groups, however, the obese group had a significant hyperinsulinemia compared to the other two groups. Moreover, the diabetic group had a significantly lower plasma insulin level until the 90 min interval and thereafter it showed a non-significant difference compared to the control group. In conclusion, both obese and diabetic rats had an impaired early-phase insulinotropic effect of GIP due to impaired gene expression of GIP-Rs which could be a potential target to prevent transition of obesity to diabetes and to improve insulin secretion in the latter.