As a pituitary hormone, prolactin (PRL) is also synthesized by immune system cells, and exerts its effects on the immune system by binding to its receptor (PRLR) via endocrine and paracrine/autocrine pathways. The immune organs adapt to the presence of fetal al -loantigens during pregnancy, and the immune system is composed of primary organs and secondary organs. The objective of this study is to analyze the effects of early pregnancy on expression of PRL and PRLR in maternal immune organs in sheep. In this study, the thymus, lymph node, the spleen and the liver were sampled at day 16 of the estrous cycle, and at days 13, 16, and 25 of pregnancy in ewes. Expression of PRL and PRLR was analyzed through quantitative real-time PCR, Western blot and immunohistochemistry. Our data showed that there were an upregulation of PRL and PRLR in the thymus, lymph node and the spleen, and a downregulation in the liver during early pregnancy in ewes. In conclusion, it is reported for the first time that early pregnancy has tissue specific effects on expression of PRL iso-form and PRLR isoform in the thymus, lymph node, the spleen and the liver, which may be owing to these organs exerting different functions during early pregnancy, and necessary for the successful pregnancy in sheep. (c) 2022 Elsevier Inc. All rights reserved.