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Chemokines and atypical chemokine receptors (ACKRs; also known as chemokine decoy receptors) play an important role in reproductive immunology by recruiting leukocytes during early pregnancy. The aim of this study was to determine the expression of C-C motif chemokine ligand 2 (CCL2) and ACKRs in the endometrium during estrous cycle and early pregnancy, and to investigate the functional effects of CCL2 on porcine uterine luminal epithelial (pLE) cells. Our results indicated that CCL2, ACKR1, ACKR3, and ACKR4 were strongly detected in the glandular and luminal epithelium of the endometrium during early pregnancy compared to that in non-pregnant pigs. Recombinant CCL2 improved pLE cell proliferation via activation of the PI3K and MAPK pathways and suppression of endoplasmic reticulum (ER) stress by reducing the expression of ER stress regulatory genes. Collectively, these results provide novel insights into CCL2-mediated signaling mechanisms in the porcine endometrium at the maternal-fetal interface during early pregnancy.CCL2-ACKR system is regulated in the porcine uterine endometrium.CCL2 induces the proliferation and cell cycle progression of porcine uterine cells.CCL2 activates PI3K/AKT and MAPK pathways for cellular proliferation in the uterus.CCL2 reduces ER stress regulatory gene expression in porcine luminal epithelia cells.CCL2 may play an important role in maternal-fetal interaction during early pregnancy.