Background: Estrogen hormone and receptors (ER) play an important role in maintaining vaginal                     health. Therefore, their disruption may adversely affect vaginal structure and function. Limited studies are available investigating the effects of diabetic complications on ER expression and distribution in the vaginal wall. Aim of the Work: This work aimed to study the effects of diabetes-induced changes on the vaginal structure, the expression of ERα as well as to determine whether the supplementation of estradiol can ameliorate these changes or not. Material and Methods: Thirty female albino rats were divided into 3 equal groups, 10 rats each. The first was the control received the vehicle only, the second was the diabetics, received a single intraperitoneal injection of alloxan (150mg/kg), and the third was diabetic/estradiol treated. Eight week-diabetic animals were injected subcutaneously with estradiol 20μg/kg/day dissolved in peanut oil for 8 weeks. By the age of 16 weeks, the animals were sacrificed, blood samples were collected to estimate the serum estradiol level and the vagina was removed and processed for paraffin sections at 5μm thick. For routine histopathological assessment H and E was used. Masson's trichrome used for collagen fibers and estrogen immunoperoxidase stains for ERα. Results: Diabetic rats showed highly significant decline in the serum estradiol level (19.6 ± 8.4 pcg/ml) compared to the controls (126.6 ± 7.6 pcg/ml). Histopathological examination revealed thinning of the vaginal epithelial layers, increase in the collagen deposition in the submucosa, marked atrophy in the muscularis layer and decrease in ERα immunostaining. Treatment of diabetic animals with estradiol for eight weeks led to its increase to a sub-physiological level (35.1 ± 5.7pcg/ml) and marked hypertrophy of the muscularis layer and re-stratification of the vaginal epithelium. Moreover, there was marked reduction in the nuclear and cytoplasmic ERα  immunostaining in the epithelium and increase in its expression in the stroma of the lamina propria and in the muscularis layer as compared to the control group. Conclusion: Diabetes-induced structural changes in the vagina may be a consequence of decreased levels of estrogen. The increase in the estradiol level, even at a sub-physiologic level, can ameliorate these atrophic effects.