To investigate the expression of Prominin-1 (Prom-1) in mouse uterus during peri-implantation. In situ hybridization and immunohistochemical staining were used to detect the mRNA and protein expression level of Prom-1 in mice uterus in early pregnancy, pseudopregnancy, estrous cycle, treated with hormone, delayed implantation and activation models. The results showed that Prom-1 was gradually weakened in uterine luminal epithelium (LE) and glandular epithelium (GE) during days 1-4 of pregnancy. During days 5-8, Prom-1 was strongly expressed in GE, and signal of Prom-1 protein was detected in matrix and decidua around the embryo. Similar to pregnancy, Prom-1 was strongly expressed in LE and GE on the 1st day and weakly expressed on the 4th day of pseudopregnancy. In addition, Prom-1 was highly expressed in LE and GE on estrus. Expression of Prom-1 was observed in the LE and the GE of delayed-implantation uterus. In activated-implantation animal model, Prom-1 was strongly expressed in the GE. In the hormone-treated model, Prom-1 expression levels were higher in the uterus of the 17β-estradiol-treated group than those in the control group. These results indicated that Prom-1 might promote the proliferation of mouse endometrial epithelium and participate in the establishment of uterine receptivity. Meanwhile, the expression of Prom-1 was up-regulated by the 17β-estradiol, indicating that Prom-1 might involve in the process of decidua development regulated by uterine glands, and Prom-1 might play an important role in mice early pregnancy.