Characterization of dendritic cells (DC) in human diabetes has been restricted to monocyte-derived DC in type 1 diabetes, whose physiological relevance to endogenous DC is uncertain. Here, we provide the first report characterizing the phenotype and function of endogenous DC subsets in type 1 and type 2 diabetes. We show that DC subsets in each diabetic group exhibit normal properties concerning frequency and activation state, as determined using 4-color flow cytometry of whole blood cells. DC maturation is also intact as confirmed by their efficacious ability to stimulate T cell proliferation in an allogeneic MLR assay. Yet we found that DC are poor producers of IFN-alpha (P < 0.05) in human diabetes. IFN-alpha is a potent antiviral agent and therefore its reduced levels may interfere with T cell-mediated immune responses leading to increased susceptibility and persistence of infections in persons with diabetes.