- Current understanding of the mechanisms underlying renal disease in humans is incomplete. Consequently, our ability to prevent the occurrence of renal disease or treat kidney disease once it develops is limited. There are objective difficulties in investigating kidney disease directly in humans, leading investigators to resort to experimental animal models that simulate renal disease in humans. Animal models have thus been a tool of major importance in the study of normal renal physiology and have been crucial in shedding light on the complex mechanisms involved in normal kidney function and in our current understanding of and ability to treat renal disease. Among the animal models, rat has been the preferred and most commonly used species for the investigation of renal disease. This chapter reviews what has been achieved over the years, using rat as a tool for the investigation of renal disease in humans, focusing on the contribution of rat genetics and genomics to the elucidation of the mechanisms underlying the pathophysiology of the major types of renal disease, including primary and secondary renal diseases.