To determine the effect of 2-methoxyestradiol on Neointima formation after an artery injury.The experiments were performed in five experimental groups of Sprague-Dawley Rats with a body weight 180-200 g: intact female, male, ovarectomized, ovarectomized plus 2-methoxyestradiol (10 mg/Kg.h,Alzet osmotic pump) and male plus 2-methoxyestradiol. Ovarectomy and osmotic pump placement were performed one week before the femoral artery injury by an endothelial denudation with an angioplasty guide was performed. The study continues during the following two weeks. The rats were anesthetized with sodium pentothal (5mg/100g body weight) and both femoral arteries were removed after perfusion and fixation in formaldehyde 10% in PBS. Each artery was sliced into 2-mm-thick slices using a razor blade cutting device and placed into a histocasette dehidrated through a series of graded alcohols and embedded in paraffin. Bocks were sectioned at 3-4 mm using a HM310 microtome in 10 slices per artery. Structural changes (neointima-to-media ratio) were quantified by the image analyzer software (Zeiss K300). Femoral Artery injury did not induce gender significant differences in the neointima formation (1.00 ± 0.12 in female and 0.8± 0.15 in male). However, ovarectomy induced a mayor increase in neointima formation showed by a neointima-to-media-ratio of 1.42±0.12 compare to intact rats. The treatment with 2-methoxyestradiol had no effect on neointma formation in males (0.93±0.17) but this treatment prevented the greater effect on injury on neointima formation induced by ovarectomy.These results suggest that 2-methoxyestradiol is effective on neointima formation was female-specific by attenuating the more marked response in ovarectomized female rats.