This study describes changes in the pattern of microridges, keratinization, desquamation, secretion, leukocyte infiltration as well as the increasing number of mitotic cells in the vaginal epithelium of Calomys callosus during the oestrous cycle. In proestrus, the epithelium is squamous and stratified with a fine layer of keratin and it is overlain by secretory prismatic cells. In oestrous, the epithelium is squamous, stratified and keratinized. In metoestrus, the epithelium is squamous and stratified with loss of the keratin layer. A leukocyte infiltration, extending from the base to the surface of the epithelial layer is also present. At the end of this phase, the surface cells start to become PAS-positive. In dioestrus, the epithelium is stratified. The superficial cells are prismatic, exhibiting the structural and ultrastructural characteristics of glycoprotein secreting cells supported by a layer of squamous cells. At the end of this phase, kerato-hyaline granules appear in the granular layer of the epithelium, indicating the beginning of the keratinization process, present in the next proestrus.