Objective To determine whether chronic hyperglycemia causes increased levels of serum tumor necrosis factor (TNF) and interleukin 1 α (IL-1 α) and IL-1 β. Research Design and Methods Sera were obtained from 59 diabetic patients, 44 chronically ill nondiabetic patients, and 34 age-matched healthy control subjects. Mononuclear cells were isolated from a subgroup of diabetic patients and healthy control subjects. Results Except for a modest increase in the prevalence of detectable serum TNF levels in diabetic patients, the serum cytokines measured in this study did not appear to be altered in diabetes. In vitro TNF production by mononuclear cells was not altered in diabetic patients. However, in vitro IL-1 β secretion, in response to lipopolysaccharides, was reduced. Conclusions Diabetes mellitus is not associated with significant changes in serum levels of TNF, IL-1 α, or IL-1 β. In vitro secretion of IL-1 β in response to lipopolysaccharides may be reduced in diabetes.