AIM: to examine the effects of estradiol supplementation on the attenuation and reversion of renal structural changes once they have been initiated by the diabetic milieu. METHODS: Albino rats were randomly divided into two groups: Normal control and diabetic groups. The diabetic group was subdivided into 3 subgroups: 8-week diabetic group (D8), 16-week diabetic group (D16) and diabetic/estradiol treated group (D/E).   Blood glucose, estradiol level, body weight, kidney weight and fractional kidney weight were measured at the time of scarification. Kidney sections were stained with heamatoxylin and eosin and Sirius red stains. Renal expression of vimentin was determined by immunohistochemistry. RESULTS: There was significant increase in blood glucose level in all diabetic groups with no significant difference between them. Plasma estradiol level was significantly decreased in the diabetic groups. Estradiol supplementation restored the plasma estradiol level to sub-physiological level and significantly attenuated the decrease in the body weight and the increase in fractional kidney weight. Furthermore, estradiol markedly decreased the structural kidney changes caused by diabetes and inhibited the increase in the amount of collagen fibers as evidenced by the decrease in the glomerulosclerosis and tubulo-interstitial fibrosis indices. Estradiol also attenuated the expression of vimentin. Estradiol had the ability to reverse the kidney as evidenced by the significant decrease in the glomerulosclerosis index as compared with that of the 8-week diabetic group.  CONCLUSION: Estradiol supplementation can reverse the structural changes caused by diabetes after it has been initiated. It can prevent and reverse the renal fibrosis.