SUMMARY Nephropathy remains an important complication of diabetes. This work was carried out to evaluate the protective effects of N-thioacetylbiguanidine on the diabetic rat kidney. Fifteen adult male Wistar rats were divided into two groups: Group I, control (n=5) and Group II, diabetic group (n=10). The latter was equally divided into two subgroups: IIa (diabetic control) and IIb (diabetic Nthioacetylbiguanidine treated). Specimens were taken from the renal cortex, processed and examined using light, immunohistochemical, ultrastructural and morphometric techniques. The renal cortices from diabetic animals showed dilated glomeruli and tubules and thickening of the glomerular capillary basement membranes. The proximal tubules revealed partial loss of brush border and deposition of PAS-positive material in some distal tubules. iNOS-immunoreactivity was strongly expressed in the renal tubules and glomeruli. The juxtaglomerular (JG) cells revealed no intra-cytoplasmic secretory granules. The histological changes in renal glomeruli and tubules were improved in N-thioacetylbiguanidine treated group. Use of N-thioacetylbiguanidine characteristically reduced iNOS expression in kidney and renin secretion in JG cells. In conclusion, N-thioacetylbiguanidine is effective in attenuating the histological changes of diabetic nephropathy reaching healing features, which resemble that of a normal kidney.