Aspartame is an artificial sweetener usually consumed by hundreds of millions of persons all over the world. Its metabolites can be toxic to many organs and there are only a few studies on the use of aspartame during gestation. The present study was designed to fully evaluate the effect of aspartame on the histological structure of the placenta in the adult albino rat. Twenty pregnant female rats were equally divided into group I that served as control, and group II that received aspartame at a dose 14 mg/kg by gavage on the 9th, 10th and 11th day of pregnancy. Placental specimens were processed for histological and immunohistochemical staining against vascular endothelial growth factor (VEGF). Aspartame induced a significant decrease in the mean placental weight and the mean thickness of both labyrinth and basal zones. Damage in the placenta was detected in the form of rupture of the interhemal membrane, lysis of glycogen trophoblast cells, spongiotrophoblast cells with vacuolated cytoplasm and darkly stained nuclei. A significant increase in vascular endothelial growth factor expression in both labyrinth and basal zones was detected. Ultrastructural examination showed fetal capillaries with condensed nuclei of endothelial cells, cytotrophoblasts with condensed fragmented nuclei and vacuolated cytoplasm, and syncytiotrophoblasts with irregular condensed fragmented nuclei. It could be concluded that aspartame has deeply impacted the normal structure and presumably the function of the placenta, therefore, restrictions are to be imposed on the consumption of aspartame especially during pregnancy.