During implantation period uterus undergoes functional and histological changes including cell proliferation, differentiation, apoptosis. This delicate condition is regulated by various factors such as steroid hormones, cytokines, and growth factors. From previous our studies, we showed the spatio-temporal expression of Müllerian inhibiting substance (MIS) and MIS receptor Ⅱ (MISR II) in mouse uteri during pregnancy. In present study investigated the role of MISRⅡ in proliferation and differentiation in the uterus. The decidualization markers were dramatically decreased during treated rhMIS and MISRⅡ viral particles in in vitro decidualization model. The intensity of PAS staining and Oil-Red-O staining were dramatically decreased by treatment of rhMIS and overexpression of MISRⅡ. MIS/MISRⅡ also suppressed stromal proliferation regulate the differentiation of stroma cell during decidualization. MIS suppress the stromal proliferation and decidual differentiation along with its receptor. Put together it is suggested that MIS works as paracrine and autocrine factors for cell proliferation regulator and differentiation regulator during implantation.