Intrauterine administration of peripheral blood mononuclear cells (PBMCs) prior to bovine embryo transfer (ET) was previously shown to improve the pregnancy rate. To better understand how PBMCs improve the pregnancy rate, we examined gene expression in the cells from uterine lumen and evaluated the morphology of bovine pre-attachment embryos in utero following intrauterine administration of PBMCs. On day 3 of the estrous cycle (day 0 = estrous), bovine PBMCs were isolated and suspended in RPMI 1640, and were incubated for 24 hr. The cultured PBMCs were administered non-surgically to the uterine horn ipsilateral to the corpus luteum on day 4 of the estrous cycle (PBMC group). On day 9, endometrial–luminal lymphoid cells from uterine lumen ipsilateral to the corpus luteum were collected by uterine flushing. Transcripts for macrophage-colony stimulating factor in the lymphoid cells were more abundant in the PBMC group than in the control group (P < 0.05). On day 7 (of the separate experiments), five blastocysts were each transferred to the luminal area, to which PBMCs had been administered on day 4. These embryos were allowed to develop in utero until day 15 of gestation, when embryos were non-surgically retrieved from the uterus. The average length of trophoblasts recovered from the PBMC group was significantly longer than that of the control group (51.6 ± 7.8 vs. 27.4 ± 6.0 mm, P < 0.05). Our results strongly suggest that intrauterine administration of PBMCs improves endometrial environment, which promotes early development of pre-attachment conceptuses. Mol. Reprod. Dev. 77:954–962, 2010. © 2010 Wiley-Liss, Inc.