Recently, environmental nonylphenol (NP) exposure in the fetus and child has received increasing attention because of its potentially deleterious effects on the central nervous system (CNS). Microglia (MG), resident immune cells in the CNS, are vital to CNS homeostasis and defense against exogenous chemicals, which makes them a potentially sensitive target of NP. The present study aims to explore the effects of maternal NP exposure during pregnancy and lactation on MG in offspring hippocampus, the production of pro-inflammatory cytokines by MG, and associated underlying mechanisms. We found that maternal NP exposure increased the production of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in offspring hippocampus. Increases in both activation and number of MG were observed in offspring hippocampus. Increased phosphorylation of Akt was found to co-localize with hippocampal MG, while increased phosphorylation of c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) were observed in offspring hippocampus. Activator protein 1 (AP-1), an inflammatory transcription factor, was also activated in the hippocampus of pups subjected to maternal NP exposure. These results suggest that maternal NP exposure might activate MG in offspring hippocampus. This activation seems to subsequently increase the production of IL-1β, IL-6, and TNF-α. Furthermore, Akt/MAPK/AP-1 signaling may be involved in this activation of MG and increased production of pro-inflammatory cytokines.