Previous in vitro findings suggest the involvement of interleukin 1 (IL-1) in the pathogenesis of insulin-dependent diabetes mellitus. The aims of the present study were to investigate the effects of single or repeated ip injections of recombinant IL-1β on blood glucose and glucose tolerance in vivo. Normal Wistar Kyoto rats were injected ip with a single injection of 4 μg/kg of the mature form of recombinant IL-1β (amino acids 117-269) or once daily on 5 consecutive days. Control rats were given vehicle and were fed ad libitum or pair-fed together with the rIL-1β treated rats. An ip glucose tolerance test (0.2 g D-glucose/100 g) was performed 2 h after injection of rIL-1β. A single injection of rIL-1β caused a mild depression in blood glucose and an improved glucose tolerance. Multiple injections of rIL-1 β induced a diminished weight gain, a 24-28% reduction in food intake, a lasting mild depression of blood glucose (7 days) and a transiently impaired glucose tolerance on day 5. We conclude that systemic IL-1 should be considered an important regulator of glucose homeostasis in vivo.