Production of melatonin (MLT) in the pineal gland (PG) of inbred mice such as C57BI/6J, BALB/c, and AKR strains is still a matter of debate. In a recent study we validated the presence of MLT in the PG of these inbred mice. We found a short-term MLT peak in the middle of the dark period with a pattern that mirrors that found previously in the serum. In another study, based on the known immunoregulatory role of MLT, we investigated the role of the PG and MLT in autoimmune diabetes mellitus type I using, as an experimental model, female nonobese diabetic (NOD) mice. Mice were pinealectomized or treated chronically with MLT (injected subcutaneously or administered via drinking water). We found that neonatal pinealectomy accelerates the development of disease in female NOD mice, whereas exogenous MLT protects animals. This is in spite of the fact that MLT increased the production of insulin autoantibodies (IAA). We conclude that PG and MLT influence the development of autoimmune diabetes, although the mechanism of action needs further investigation.