Programmed cell death (PD) ligand 1 (PDL1) and PDL2 and their receptor PD1 play critical roles in immunity, and an involvement of the PDL1/PDL2-PD1 signaling system in the immune tolerance during pregnancy has been suggested in humans. However, the role of the PDL1/PDL2-PD1 signaling system at the maternal-conceptus interface has not been studied in pigs. Thus, this study determined the expression, regulation, and function of the PDL1/PDL2-PD1 signaling pathway at the maternal-conceptus interface in pigs. The endometrium expressed PDL1, PDL2, and PD1 mRNAs in a pregnancy stage-specific manner with greater levels of expression on Day 15 of pregnancy than on Day 15 of the estrous cycle. PDL1 protein was localized to some stromal cells and vascular smooth muscle cells, PDL2 protein to luminal (LE) and glandular epithelial (GE) and endothelial cells, and PD1 protein to LE, GE, and some stromal cells, but not in T lymphocytes and endothelial cells. The conceptus tissues during early pregnancy and chorioallantoic tissues during mid- to late pregnancy expressed PD1, PDL1, and PDL2. Interferon-γ (IFNG) increased the expression of PDL1 and PDL2, but not PD1, in endometrial explants. PDL1 and PDL2 increased the expression of inhibitors of apoptosis in porcine uterine epithelial cells overexpressing PD1. These results suggest that the expression of PDL1 and PDL2 are induced by IFNG of conceptus origin and PDL1/PDL2-PD1 signaling may play an important role in maintaining the epithelial stability by regulation of apoptosis and controlling the endometrial environment for the establishment and maintenance of pregnancy in pigs. SUMMARY: The PDL1/PDL2-PD1 signaling system induced by conceptus-derived IFNG plays an important role in maintaining endometrial epithelial stability by increasing the epithelial expression of inhibitors of apoptosis during early pregnancy.