This study was designed to investigate the effect of the methanol root extract of Cissampelos mucronata on the histology of the ovaries and uterus as well as the oestrus cycle. A total of 25 female rats were used for this study. The rats were randomly divided into groups of 5 rats  per dosage group (I-V). Group I served as the control group and were administered normal saline equivalent to the volume administered to the highest dosed experimental rats. Rats in Groups II, III and IV were administered with 100 mgkg-1, 200 mgkg-1 and 300 mgkg-1 doses of the extract respectively while rats in Group V were administered the highest dose (300 mgkg-1) of the extract for 20 days and allowed to stay for at least 14 days post treatment to observe for reversibility, persistence or delayed occurrence of toxic effects. The result of this study showed that administration of the methanolic extract of the root of Cissampelos mucronata in rats caused loss in body weight, degenerative changes in  Graafian follicles, inflammatory cells, degenerating follicles, proliferation of granulosa cells and atretic follicles with uterine tissues characterized by mild to moderate stromoglandular dissociation, focal areas of necrosis, proliferation of connective tissue stroma and alteration in estrous cycle length, characterized by prolonged metesterus and diestrus phases with no effect on progesterone, Luteinizing Hormone(LH) and Follicle Stimulating Hormone (FSH) levels. The study revealed significant alterations in histological and hormonal profile of female rats. It is recommended that full stereology studies be carried out.