It has been suggested that there exists a local immune-neuroendocrine self-regulating system in the pancreas. The system consists of beta-cells, nerve ganglia, intercellular fluid, connective tissue, and endothelial and immunocompetent cells. The local immune-neuroendocrine system governs the background level of insulin production by intrinsic mechanisms both in normal conditions and in a recovery period after different kinds of stress. The activity of this system by a complex of metabolic, environmental, nerve, and nonspecific immune factors has been determined. The local immune-neuroendocrine system is partially autonomous as a result of local integrative nerve circuits, morphological and functional substrates. Increased or decreased synthesis and release of some cytokines or biologically active substances (neurotransmitters, neuropeptides, gamma-aminobutyric acid, metabolites, nitric oxide, ions, etc.) by various cell types in the local immune-neuroendocrine system above usual levels may result in disturbances of sensitivity and functions of beta-cells. If the capability of the local immune-neuroendocrine system is insufficient for their compensation, the islet cell autoantigens may occur, the specific immune mechanisms are involved, and the pathological process becomes irreversible. Some ways for prevention of disturbances in the local immune-neuroendocrine system during the early and late phases of diabetes are presented.