A comprehensive understanding of the pathogenic mechanism is the prerequisite for proper disease management. However, the mechanisms of diabetes mellitus and diabetic complication remain extremely complicated and unresolved. While immune reactions are involved in the pathogenesis of diabetes and diabetic complication, the diabetic condition itself can influence immune responses. Furthermore, both diabetes and immune reactions are regulated by genetic and environmental factors. As a result, animal models have evolved to be powerful research tools to elucidate the complicated mechanisms for the pathogenesis of diabetes. Recently, various animal models of diabetes have been developed in rats, which provide advantages over mouse models in the scale of tissue samples and variation in type 2 diabetes models. In this review, we introduced rat models of diabetes and summarized the immune reactions in diabetic rats to propose the relationship between immune reactions and diabetes. Type 1 diabetes is induced by self-reactive cellular immune reactions. On the other hand, type 2 diabetes in rat models is associated with augmentation of innate immune reactions and increased humoral immunity. For example, helper T (Th) 1/Th17 cells are prevalent in non-obese type 1 diabetes rats (diabetes-prone BioBreeding rats), while non-obese type 2 diabetes rats (Goto-Kakizaki rat) show higher levels of natural IgM and T cell ratios with elevated Th2 cells compared with Wister rats. The investigation of immunological disorders in various diabetic rat models is useful to elucidate complicated mechanisms for the pathophysiology of diabetes. In future studies, immunological experimentations altering Th1/Th17 or Th2 cell levels and natural immune reactions may lend support to understanding the causes of diabetes and predicting the pathological conditions in diabetes.
