Mast cells are engaged in the body’s inflammatory response, which seems to require an invasion of foreign materials. These cells reside in connective tissue and mucous tissue that encircle the internal environment of the body. Mast cells also can be found in uterus tissue, which is in fact exposed to the external world. Due to the mast cells’ role in the inflammatory response when they meet invading foreign cells, they will attempt to block the invasion of sperm and fertilized eggs, which are ultimately foreign to the female body. Thus, the inflammatory response by the mast cells should be controlled if there is to be successful fertilization and implantation of an egg. In order to confirm such an assumption, we investigated the changes in mast cell numbers in rat uteruses and sex hormone concentration during their estrus cycles. The mean numbers of mast cells at the proestrus and estrus phases were 4.8±2.72 and 5.98±1.55, respectively. The number increased as much as 3 times more than the mast cells that are generally found in such barrier tissues as skin, mucous surfaces of the respiratory system, the intestines and the uterus which surround the internal body environment. Within this tissue, mast cells are distributed in close association to the smooth muscle and fibroblast cells. The density and distribution of mast cells are apt to change in response to internal and external signals. Mast cells within the uterine tissue are expected to be under the influence of reproductive cycle because this organ shows dramatic changes through the reproductive cycle. In this study, changes in distribution and density of uterine mast cells were correlated to hormonal changes and uterine tissue development in rats. The concentration of circulating Estradiol-17β was lowest at the metestrus phase, both in free and bound form. The results suggest that estrogen may be involved in suppressing the number of mast cells in the uterus during the critical time of egg fertilization and implantation.