Diabetic nephropathy (DN) pathogenesis is very complex and multifactorial. There are several mechanisms or pathways that hyperglycemia leads to renal injuries. Each pathway makes renal injuries via several mediators. Some mediators are common between the pathways such as reactive oxygen species (ROS) and TGF-β and there are many overlaps and interference between the pathways. This review summarized complexity of DN pathogenesis and overlaps or interfering of mediators between the pathogenesis pathways. Besides, in the review suggested new designs of researches based on this complexity pathogenesis. The pathogenesis of DN is certainly very complex and multifactorial. From the overview of molecular mechanisms of DN pathogenesis, there are many pathways and many mediators with many interferences and overlaps between them. The focal point of this pathogenesis still unknown but it seems that RAAS system, oxidative stress and TGF-β relatively are common between these complex tangle webs of pathogenesis.