Attachment to endometrial epithelium is an essential process for human embryos. Although it is widely accepted that this process is largely regulated by the endocrine system, the precise molecular mechanism(s) remains unclear. Recent evidence suggests that immune cells actively contribute to the establishment of embryo implantation. In accordance with this, we found that peripheral blood immune cells positively affect the differentiation of maternal endometrium to facilitate embryo implantation during early pregnancy. From these findings, we propose a novel concept that circulating immune cells are important regulators of embryo implantation. Lately, implantation failure in patients treated with in vitro fertilization and embryo transfer has received increasing attention. Based on our hypothesis, we have successfully developed a new therapy for implantation failure using autologous peripheral blood immune cells. These findings suggest that supportive mechanisms via the immune system facilitate embryo implantation and will be useful in the field of assisted reproductive technology.