Diabetes and its complications have become a public health problem. One of the most important complications is diabetic nephropathy, which is nowadays the main cause of chronic renal failure. In spite of our greater understanding of this complication, the intimate mechanisms leading to the development and progression of renal injury are not well understood. New perspectives in activated innate immunity and inflammation appear to be relevant factors in the pathogenesis of diabetes. Moreover, different inflammatory molecules, including adipokines, Toll-like receptors, chemokines, adhesion molecules and pro-inflammatory cytokines, may be critical factors in the development of microvascular diabetic complications, including nephropathy. This new pathogenic perspective leads to important therapeutic considerations, with new pathogenic pathways becoming important therapeutic targets that can be translated into clinical treatments for diabetic nephropathy.