Abstract: Female reproductive physiology is highly complex not the least because of the necessity of direct interaction and integration between the fetus and the mother. An example is the role of inflammatory processes, which seem to be necessary at the beginning of pregnancy and a thread for the continuation of pregnancy later in the gestational period. Comparative work in the gray short tailed opossum, Monodelphis domestica, a marsupial with very short period of direct fetal-maternal contact in the uterus, suggests that inflammation was ancestrally present because of the effect of embryo attachment on the uterine mucosa. Never the less, the hypothesized ancestral inflammatory reaction was modified, both in the marsupial and the placental mammalian lineage. Specifically in Monodelphis, the inflammation seems to be supported by both the maternal as well as the fetal tissues [cooperative inflammation] and likely plays a role in effecting parturition. In placental mammals the inflammatory reaction evolved to exclude neutrophil infiltration, and ultimately leads to an anti-inflammatory regime at the fetal maternal interface. We propose that the initial function of the decidual stromal cell, a cell type that only exists in placental mammals, was to mediate the switch from the inflammatory to the anti-inflammatory phase of embryo implantation. Our results suggest that generic anti-inflammatory treatment at the beginning of pregnancy (during implantation) might be counterproductive, but may be compatible with normal physiology if deemed necessary later in pregnancy.