Human endometrium expresses numerous genes to achieve an optimal uterine environment for implantation and maintaining the pregnancy. In this review, we will summarize our previous observations on progestin regulated gene expression, estrogen metabolic enzymes, nitric oxide synthase, aromatase, IGF-I and II, IGFBP-1, prolactin and glycodelin. These genes are differentially activated in two types of endometrial cells during the menstrual cycle and early pregnancy. Multiple gene activation driven by progestin appears to be the major event responsible for the differentiation of endometrial cells. They play critical roles of endometrial cell function during implantation and pregnancy.