Background: The majority of cardiovascular diseases occurs in the post-menopausal period. The loss of estrogen associated with menopause can increase the prevalence of various cardiovascular disease risk factors, including hypertension, atherosclerosis, hyper-triglyceridemia and diabetes. Aim of the Work: This study was done to elucidate the effect of ovariectomy and estrogen replacement therapy on the wall of the thoracic aorta in the adult female albino rat. The study included light and electron microscopic methods. Materials and Methods: 30 female adult albino rats (6 months old) were obtained from the laboratory animal house, Faculty of pharmacy, Zagazig University. These animals were equally divided into three groups; every group contains 10 animals. Control (normal) Group, Ovariectomized Group (OVx group) and treated ovariectomized Group (OVx+E2 group) received 17β-Estradiol (E2) (15 μg/ kg/day sc) after ovariectomy was done.  All rats were weighed weekly during the experimental period. At 13th week after surgery, thoracic aorta specimens were taken for histological and electron microscopic examination. Results: At the beginning of the study, the body weights of all rats did not greatly differ among the three groups. In the 13th week, the body weight of the OVx rats increased from 195±3.4 g prior to surgery to 265±8.5 g at 13th week post-operative. However, in the treated ovariectomized (OVx+E2) group, the increase in weight was regular and similar to the control group. Under light and electron microscopes, the wall of the thoracic aorta normally consisted of three tunics: Tunica intima, tunica media and tunica adventitia. In the Ovariectomized (OVx) group, ovariectomy resulted in disruption of the intimal layer, even irreversible necrosis of the endothelium, corrugation of the internal elastic lamina in zigzag form with irregularity of its inner border, swelling of endothelial cells and alteration of the endothelial cell ultra-structure (mitochondrial swelling, cytoplasmic vacuolization and collagen accumulation). However, in treated ovariectomized (OVx+E2) group, the wall of the thoracic aorta was seen similar to the normal control and showed no obvious ultra-structural changes. Conclusions: In the ovariectomized rats, estrogen deficiency leads to increased body weight. Also, ovariectomy changes in the TI/TM ratio and these findings may be indicators of early atherosclerosis. These changes did not occur in the treated ovariectomized rats. Also, the present study suggested that the ovariectomy may induce irreversible damage to the structure of the endothelium but 17β-estradiol treatment elicits a protective effect on the endothelium