Introduction of semen into the female reproductive tract may induce molecular and cellular changes facilitating conception and pregnancy. Because prostaglandins (PGs) and appropriate vascularization of the endometrium are crucial for pregnancy success, the effect of seminal plasma (SP) on PG synthesis and angiogenesis was investigated. Gilts at estrus received an infusion of 100 ml of either SP or PBS (control). Uterine horns were collected on Days 1, 3, 5, and 10 after each treatment. Concentrations of PGE₂, PGF_2alpha , and PGFM were measured in the uterine lumen and endometrial tissue. Expression of PG synthesis pathway enzymes and angiogenic factors, infiltration of immune cells, and vascular bed development were assessed. One day after SP infusion, the PGE₂:PGF_2alpha ratio in the uterine lumen was lower than in controls. In endometrial tissue, however, PGE₂ levels and the PGE₂:PGF_2alpha ratio were elevated on Day 10. PG-endoperoxide synthase expression in the endometrium was up-regulated on Day 1 and decreased on Day 5 after SP treatment compared to that in controls. PGF_2alpha synthase levels were decreased on Day 5 and 10 in SP-treated animals when compared to controls. SP-induced vascular bed development was apparent shortly before the time corresponding to maternal recognition of pregnancy in the pig. Together, these data indicate that the porcine uterus can be sensitized shortly after SP exposure to evoke prolonged effects on PG synthesis and angiogenesis in the endometrium, persisting over the course of the prereceptive phase. Thus, SP can affect uterine receptivity and embryo-maternal interactions in pigs through locally direct and/or indirect mechanisms.