OBJECTIVE: To detect and evaluate the risk of diabetic nephropathy in its early onset. STUDY DESIGN: Glomerulopathy was detected and evaluated histologically by comparing the glomerular sizes in 10- and 20-week-old control and leptin-deficient ob/ob mice, which develop severe type 2 diabetes. In addition, the renal hyperfiltration was evaluated by comparing the perfusion- and immersion-fixed renal specimens. RESULTS: It is noticed that the glomerular sizes were significantly different among the regions of the renal cortex, even in the control mice. The renal corpuscles in the inner region were bigger than those in the middle and outer regions. When the corresponding regions were compared, the glomerular size increased significantly in ob/ob mice and in perfusion-fixed groups. The glomerular hypertrophy and hyperfiltration were more evident in the outer region of the cortex. CONCLUSION: These results show evidence of glomerular hypertrophy and the necessity of fully verifying the normal condition of the kidneys in the controls. The renal corpuscle in the outer region is suggested to be a sensitive landmark of both structural and functional damage in diabetes mellitus. © Science Printers and Publishers, Inc.