Changes in circulating cyclo(His-Pro) (CHP) levels after ingestion of 0.5 g/kg of glucose (oral) were measured in 32 Sprague Dawley rats at varying time points between 0 (before glucose) and 60 minutes. Each rat provided one time point. CHP levels displayed a biphasic response rising from 933 +/- 56 pg/ml to 1083 +/- 287 pg/ml (p greater than 0.05), followed by a fall to 543 +/- 46 pg/ml (p = 0.002) and then a recovery to near baseline values. To further investigate this response, a separate group of rats were sampled sequentially after 3 g/kg oral glucose (n = 7), 0.6 g/kg I.V. glucose (n = 6) or controls given saline only (n = 14). CHP levels were significantly elevated in the oral glucose group at 5 (p = 0.048) and 12 (p = 0.02) minutes compared to controls, while the i.v. glucose group was not statistically different from controls. Comparison of the mean of the highest incremental response to baseline values in each group revealed a greater excursion in CHP levels after oral (p = 0.027) glucose than after I.V. (p = 0.08) glucose. These data suggest CHP is acutely and reversibly elevated after glucose ingestion in rats and that the response is greater after oral glucose than after i.v. glucose.