During pregnancy, infection or immune responses induce cytokine release, which might influence fetal neurodevelopment, leading to neurodegenerative disease in adulthood. Since the hippocampus is a key area for learning and memory, we evaluated 4- and 24-wk-old rats for the effects of early and late prenatal exposure to interleukin-6 (IL-6) on hippocampal morphology, expression of mRNA for IL-6, the gamma-aminobutyric acid receptor (GABA_A5), the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor, and glial fibrillary acidic protein (GFAP), caspase-3 protein and mRNA levels, and learning abilities. Late exposure increased serum IL-6 and hippocampal expression of IL-6 mRNA at 4 and 24 wks. All adult rats showed neuronal loss in the hilus and astrogliosis; males had losses mainly in CA2 and CA3, and females in CA1. Expression of GABA_A5, NR1, and GFAP mRNA increased in late-exposed males and females at 4 and 24 wks. mRNA and protein levels of the apoptosis marker caspase-3 were increased in all late-exposed rats except males at 4 wks. Evaluation of hippocampus-dependent working memory in the Morris water maze at 20 wks of age showed increases in escape latency and time spent near the pool wall in all IL-6 adult rats, especially females. These findings suggest that fetal IL-6 exposure, especially in late pregnancy, leads to increased IL-6 levels in the circulation and hippocampus, abnormalities of hippocampal structural and morphology, and decreased learning during adulthood.