This study evaluated the in vivo effects of endotoxin and interleukin 1 (IL-1) on in vitro insulin secretion from perfused rat pancreases and isolated pancreatic islets. Glucose-induced insulin secretion was potentiated in pancreases obtained from rats 3 h after endotoxin or 30 min after IL-1. Studies using isolated pancreatic islets indicated that islet sensitivity to glucose was increased by either endotoxin or IL-1 to a similar extent, but there was no effect of endotoxin or IL-1 on the maximal insulin secretory response of islets to glucose. Insulin secretion was not potentiated in perfused pancreases obtained from rats only 30 min after treatment with endotoxin. These results suggest that in vivo treatment with either endotoxin or IL-1 potentiates insulin secretion by increasing islet sensitivity to glucose. In addition, because endotoxin is known to potently stimulate the production and secretion of IL-1 in vivo, the results lend support to the hypothesis that the effects of endotoxin on insulin secretion may be mediated partially by IL-1.