The placenta facilitates the exchange of nutrients and wastes in an effort to promote fetal development. Disruptions in the establishment of the placenta and its interactions with the maternal uterus are potential causes of pregnancy failure. In this study we investigated the pregnancy phenotype of two inbred rat strains: the Dahl Salt Sensitive (DSS) strain and the Brown Norway (BN) strain. The DSS strain is reported to have large litters, whereas the BN strain has small litters. Pregnant female rats of each strain were killed on various days of gestation. At the time of killing, the number of viable versus dead and/or resorbing conceptuses was determined. Placental tissues from viable conceptuses were collected and processed for biochemical and histologic analyses. The number of viable conceptuses at Days 8.5 and 18.5 of gestation was significantly greater in DSS versus BN rats. Additionally, the number of resorbing and/or dying conceptuses was significantly greater in the BN strain than in the DSS strain. Maternal responses to pregnancy and elements of placental and fetal development in DSS and BN rats differed. Immunohistologic analysis of placentation and gene expression profiles revealed that trophoblast cell invasion into the uterine mesometrial compartment was significantly less in the BN strain versus the DSS strain. In contrast, the uterine natural killer cell population was reciprocally expanded in the BN strain. The impairment in trophoblast cell invasion in BN rats was associated with a smaller junctional zone compartment of the chorioallantoic placenta. Collectively, the data indicate that BN rats exhibit a unique form of placentation and may represent an excellent model for investigating the genetics of placental development.