The clinical manifestations of diabetic nephropathy are similar in type 1 and type 2 diabetes, while the renal lesions may differ. Indeed, diabetic glomerulopathy is the predominant renal lesion in type 1 diabetes, although also tubular, interstitial and arteriolar lesions are present in the advanced stages of renal disease. In contrast, in type 2 diabetes renal lesions are heterogeneous, and a substantial number of type 2 diabetic patients with diabetic kidney disease have mild or absent glomerulopathy with tubulointerstitial and/or arteriolar abnormalities. In addition, a high prevalence of non-diabetic renal diseases, isolated or superimposed on classic diabetic nephropathy lesions have been reported in patients with type 2 diabetes, often reflecting the bias of selecting patients for unusual clinical presentations for renal biopsy. This review focuses on renal structural changes in type 2 diabetes, emphasizing the contribution of research kidney biopsy studies to the understanding of the pathogenesis of DKD and of the structural lesions responsible for the different clinical phenotypes. Also, kidney biopsies could provide relevant information in terms of renal prognosis, and help to understand the different responses to different therapies, especially SGLT2 inhibitors, thus allowing personalized medicine.