To explore the effects of the death receptor (mouse killer, MK) of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on decidualization of mouse uterine stromal cells, both of the over-expression and siRNA of MK gene recombinant adenovirus were applied to infect the primary culture of mouse uterine stromal cells followed by decidualization induction with estrogen, progesterone plus cAMP. Seventy-two hours later, immunocytochemical assay and flow cytometry were used to detect the prolactin protein expression and apoptosis of decidualized cells, which were transfected with MK recombinant adenovirus (overexpression and RNAi). Moreover, each MK recombinant adenovirus was injected into the uterine horns of mice on the early morning of d4 of pregnancy. The number of implanting embryos was counted on d8 of pregnancy. The results showed that the levels of prolactin protein decreased significantly, but the apoptosis rate increased in the decidualized cells transfected with MK over-expression adenovirus. In the MK siRNA group, the prolatin levels were increased while the apoptosis rate was downregulated markedly. However, uterine injection of either the over-expression or the siRNA adenovirus led to dramatic decline the numbers of the implanting embryos. These results suggested that MK was involved in modulating the decidulization of mouse uterine stromal cells possibly through balancing proliferation and apoptosis of the decidualized cells.