Context: Euphorbia hirta L. has been wildly used for its health benefits. It has been used as a decoction and to treat diarrhea, peptic ulcers, menstrual problems and venereal diseases. Aims: The study aims to investigate the estrogenic effects of E. hirta on ovariectomized (OVX) rats. Methods: The ovariectomized rats were divided into four groups, including those that received the vehicle (1% v/v Tween 80, p.o.), 17β-estradiol at a dose of 0.01 mg/kg B.W. and the ethanolic extract of E. hirta at the doses of 100 and 500 mg/kg B.W. These were administered daily for 14 days. Estrogenic activity was determined by analyzing the body, vaginal and uterine weight as well as the uterine and vaginal histopathology characteristics of the estrogen-induced response. Results: At the dose of 500 mg/kg B.W., the plant extract produced a significant increase in vaginal weight when compared with the ovariectomized rats, a slightly increase in the uterine weight and could induce hyperplastic epithelium and endometrial thickness of the vagina. Conclusion: The data in this work suggests that the plant crude extract showed weak estrogenic effects in ovariectomized rats and could be useful for health benefits for vagina atrophy of females during the menopause.