Abstract: Many species exhibiting hemochorial placentation experience an accumulation of macrophages in the endometrium during pregnancy. For the present study, it was tested whether macrophages also accumulate in the endometrium of the sheep, which is a species undergoing an epitheliochorial placentation. An additional objective was to determine whether regulation of endometrial macrophage number occurs via systemic or local signals and whether progesterone is one of these signals. The approach was to evaluate presence of macrophages immunohistochemically using antibodies to CD68 and CD14. Tissues examined were from cyclic ewes in the luteal phase of the estrous cycle, unilaterally-pregnant ewes at day 140 of pregnancy in which pregnancy was surgically confined to one uterine horn, ovariectomized ewes, and ovariectomized ewes treated with progesterone for 44 days. Macrophages were localized predominately to the stromal compartment of the stratum compactum region of the endometrium. In non-pregnant ewes, macrophages were not abundant regardless of physiological status. Increased numbers of endometrial macrophages were seen for both the pregnant and non-pregnant uterine horns of unilaterally pregnant ewes. Numbers of macrophages were higher in the endometrium from the pregnant uterine horn than from endometrium from the non-pregnant uterine horn. Results indicate that macrophages accumulate in the endometrium by day 140 of pregnancy in the sheep and that this induction is because of both systemic and local signals. Progesterone appears not to be an important regulator of numbers of endometrial macrophages.