Type 1 diabetes is an autoimmune process predominantly T-cell mediated. CD26 plays a role in T-cell costimulation, migration, memory development, thymic maturation and emigration patterns. In peripheral blood from 55 patients with type 1 diabetes and 20 healthy controls, CD4+ and CD8+ T cells expressing CD26 were differentiated into naïve (N, CD45RA+CCR7+), central memory (CM, CD45RA-CCR7+), effector memory (EM, CD45RA-CCR7-), and terminally differentiated effector memory (TEMRA, CD45RA+CCR7-). In type 1 diabetes, CD4+ and CD8+ T cells expressing CD26 showed a distinctive differentiation profile: percentages and absolute numbers of CM and N cells were reduced, whereas those of TEMRA cells were markedly increased. The indices of intermediate- and long-term glycaemic control were associated negatively with the number of CM and N cells while positively with the number of TEMRA cells. The considerable accumulation of TEMRA T cells in our patients suggests life-long stimulation by protracted antigen exposure (viruses, other agents or residual self-antigens?) or a homeostatic defect in the regulation/contraction of immune responses.