During pregnancy and the postpartum period, the adult female brain is remarkably plastic exhibiting modifications of neurons, astrocytes and oligodendrocytes. However, little is known about how microglia, the brain's innate immune cells, are altered during this time. In the current studies microglial density, number and morphological phenotype were analyzed within multiple regions of the maternal brain that are known to show neural plasticity during the peripartum period and/or regulate peripartum behavioral changes. Our results show a significant reduction in microglial density during late pregnancy and the early-mid postpartum period in the basolateral amygdala, medial prefrontal cortex, nucleus accumbens shell and dorsal hippocampus. In addition, microglia numbers were reduced postpartum in all four brain regions, and these reductions occurred primarily in microglia with a thin, ramified morphology. Across the various measures, microglia in the motor cortex were unaffected by reproductive status. The peripartum decrease in microglia may be a consequence of reduced proliferation as there were fewer numbers of proliferating microglia, and no changes in apoptotic microglia, in the postpartum hippocampus. Finally, hippocampal concentrations of the cytokines interleukin (IL)-10 and IL-6 were increased postpartum. Together, these data point to a shift in the maternal neuroimmune environment during the peripartum period that could contribute to neural and behavioral plasticity occurring during the transition to motherhood.