Background: Recently, there are several reports that diabetic hyperglycemia is not only the consequence of insulin deficiency but also affects the functions of pancreatic islets. The cnntroversies of hyperglycemic effects on islet function are mainly due to the duration of exposure to hyperglycemia and other modifying factors such as interleukin-1 beta which may influence the islet functioins. In the present study, we observed the effect of hyperglycemia and combined effect of hyperglycemia and inter Ieukin-I beta on the insulin secretion of rat islets for short-term and long-term period by long-term culture system which we have recently establishied. Method: we obtained pancreatic islets of male Sprague-Dawley rats, weighing 80--100g, isolated by collagenase method and Ficoll density gradient centrifugation method. To observe the effect of a few days exposure to hyperglycemia, islets were cultured for 2 or 3 days in culture medium RPMI 1640 containing 1.1 or or 27,7 Mm/ L glucose. Thereafter islets were cultured for 6 days with daily change of culture media with 1.1 Mm/ L glucose. To investigate the relationship between dose of 1L-1 and various glucose concentrations, islets were cultured in medium RPMI 1640 containing various concentrations of glucose (2.8, 5.5, 11.1 and 22.2 Mm/L), with or without IL-1B (0, 5 Pm, 2 Nm) for 14 days. We measured total accumulated insulin secretion every day by RIA method. Result: 1) Threshold level of glucose stimulated insulin secre tion of islets is above 5,5 Mm. 2) A period of three days exposure to high glIucose concentration did not seern to impair the function of. Islets in terms of insulin secretion. 3) Clucose and IL-1B stimulated the ineulin secretion of islets as dose dependent manner for the first 2 hours. But, insulin secretion was markeldy suppn",ssed by high dose of IL-1B at 24 hours. 4) ln a low dose of IL-1B, glucose was dominant stimulator on the insulin secretion of islets and that in high dose of Ll-1B, marked inhibitory aetion on thc insulin sectetion of islet. Was evident regardiess of glucose concentratiions during long-term culture. Conclusion: Glucose concentration is thought to be an important determinant of interleukin-1 beta effect on insulin secretion and bimodal effect of interleukin-I beta on the glucose stimulated insulin secretion of islets was evident. The effect of interleukin-I beta on the insulin secretion of islets depend on its concentration, duration of exposure and concentration of g1ucose Further studies are needed to understand underlying mechanisms of these effects of interleukin 1 beta and glucose on the islets in vitro.