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Interferon-tau (IFNT) is the main signal for maternal recognition of pregnancy in ruminants. IFNT acts on the endometrium, corpus luteum, and liver through paracrine and endocrine style, which is involved in inhibiting the development of luteolytic mechanism and suppressing maternal immune rejection of the semi-allogeneic fetus. Bone marrow (BM) is a key component of the lymphatic system, supports the body’s immune system through producing the lymphocytes. At present study, the BM was obtained from days 13, 16 and 25 of pregnant ewes, day 16 of non-pregnant ewes to study the expression of interferon stimulated gene 15 kDa protein (ISG15) mRNA and protein through a qRT-PCR assay, Western blot, and an immunohistochemistry analysis. Our results showed that the expression of ISG15 mRNA, proteins and conjugated proteins were up-regulated in the stroma of BM during early pregnancy, and the immunohistochemistry results confirmed that the ISG15 proteins were localized in the cytoplasm of different cells in the stroma of BM. In conclusion, IFNT derived from the conceptus induced upregulated expression of ISG15 and conjugated proteins in the stroma of BM through an endocrine style, which were involved in regulating the maternal immune response during early pregnancy in ewes.