In type 1 diabetes mellitus (T1DM), cytokines can be directly cytotoxic to beta-cells, and/or play an indirect role influencing some cells of the immune system. Since several factors could impair cytokine serum levels, the purpose of our study was to longitudinally evaluate intracellular cytokines, in T1DM patients, and in subject at risk, by flow cytometry analysis. At T1DM onset we observed significantly lower percentage of peripheral CD4 + and CD8 + cells producing IFN-gamma in patients compared to controls and subjects at risk. The 15-month follow-up patients showed significantly lower percentage of CD4 + and CD8 + cells producing IFN-gamma compared to the other groups. At 8-year follow-up no significant differences were observed among the groups in the percentage of cells producing cytokines. We could have considered "exhausted cells" or these T cell subsets may be migrated from peripheral blood to pancreas. On the other hand, our results are in agreement with those reported in literature: in animal model the absence of IFN-gamma production makes beta-cells highly susceptible to viral infection and subsequent attack by natural killer cells, which lead to hyperglycaemia and diabetes mellitus.