Genistein is naturally occurring in plants and binds to estrogen receptors. Humans are mainly exposed through diet, but the use of supplements is increasing as genistein is claimed to promote health and alleviate menopausal symptoms. We analyzed diverse uterine features in adult mice chronically fed genistein for different times. The luminal epithelium height was increased in females treated with 500 and 1000 ppm at PND 95, and the width of the outer myometrium was increased in females treated with 1000 ppm at PND 65 compared to that in controls. An increase in proliferation was noted in the inner myometrium layer of animals exposed to 300 ppm genistein at PND 185 compared to that in controls. Luminal hyperplasia was greater in the 1000 ppm group at PND 65, 95, and 185, although not statistically different from control. These results indicate that genistein may exert estrogenic activity in the uterus, without persistent harm to the organ.