Interleukin-1 (IL-1), a cytokine mainly produced by monocytes-macrophages, plays a crucial role in immunological and inflammatory processes. We have recently demonstrated that IL-1 can also affect neuroendocrine mechanisms. In this paper, we refer to the capacity of IL-1 to affect glucose homeostasis. In normal mice, low doses of IL-1 induce a long-lasting hypoglycemia which is not dependent on possible insulin-secretagogue actions of this cytokine. The hypoglycemic effect of IL-1 is also observed in insulin-resistant diabetic mice. Furthermore, IL-1 seems to adjust the ‘set point’ for glucose regulation to a lower level. The effects of IL-1 on glucose homeostasis constitute a clear example of the biological relevance of immune-neuroendocrine interactions.