The uterus is a very important reproductive organ for implantation and holding embryos till labor. Many drugs and medicinal plants affect the uterus, some researchers reported that Salvadora persica (Miswak) is a phytoestrogen plant as it contains flavonoids and can be used as a contraceptive drug; however, no available investigations explain the histomorphological structure of the uterus after Miswak extract administration. Twelve female albino rats (165.3 ± 3.269 g) were divided equally into two groups.  In the control group, the animals received normal saline daily for 4 weeks. While in the Miswak treated group, the animals received 900 mg/kg of body weight of the Miswak aqueous extract daily for the same period. Grossly, at the end of the experiment, our results revealed that the uteri in the Miswak-treated group had characteristics of low active organs; they were pale with low weight and high thickness. In contrast to the treated group, the uteri of the control group had the signs of active organs; they were more vascular, relatively thin and edematous. Microscopically, in the control group, the uterine lumen was wide and the mucosa was folded and covered by secretory columnar epithelium. The uterine glands were more active, and the myometrium was thick. Whereas, in the Miswak-treated group, the lumen was slit-like, the uterine glands were less active, and the uterine wall had thick lamina propria and thin myometrium. In conclusion, the oral administration of Miswak extract reduces the uterus activity. It showed a state of anestrous with a narrow slit-like lumen and a decrease in glandular activity.