The mouse uterus undergoes continual histological and immunohistochemical changes during the estrous cycle; these changes are regulated by the levels of ovarian hormones. Connective tissue growth factor (CTGF), one of the first CCN members, is a multifunctional signaling modulator participating in a wide variety of physiological and pathological processes, such as angiogenesis, osteogenesis, renal disorders, and carcinogenesis. By using histological and immunohistochemical investigations, this study is to focus on the changes of the expression levels of CTGF which are synchronized with the histological changes of the mouse endometrium during the estrous cycle. At proestrus, the luminal epithelium is columnar, the uterine glands are many and distributed evenly throughout the mucosa, at estrus, the luminal epithelial cells are columnar and the lumina of uterine glands are wide pointing to functional activity. Metestrus showed degeneration of endometrial columnar epithelium cells and endometrial atrophy continued degeneration of endometrial epithelial cells. At the diestrus, luminal epithelium is low columnar and has no basement membrane. Moreover, CTGF expressed strongly in the stroma of the endometrium, the connective tissue and blood vessels of myometrium and perimetrium at proestrus and estrus phases. At metestrus, the expression of CTGF was reduced to extremely low level in the endometrial stromal cells. In contrast, CTGF was expressed moderately in the perimetrium, and in endometrial blood vessels and the connective tissues of myometrium. At the diestrus, CTGF was expressed strongly in the blood vessels of endometrium and myometrium and expressed moderately in the stromal cells of endometrium. The luminal epithelium and uterine glands showed weak signal. Taking together, our results suggested that the growth of the endometrial stroma and blood vessels is associated with the strong expression level of CTGF during the proestrus and estrus phases.