Chronic neuroinflammation is associated with many neurodegenerative and neurocognitive disorders, yet few animal models exist to study the behavioral effects of prolonged neuroinflammation. Therefore, we recently developed a transgenic mouse model harboring an interleukin-1β excisional activation transgene (IL-1β(XAT)). These mice display localized IL-1β overexpression and resultant neuroinflammation for up to 1 year following transgene induction. Initial behavioral studies demonstrated long-term memory deficits after 2 weeks of hippocampal IL-1β overexpression. In the present studies, we extend these behavioral studies both in scope and timing. We find long-term contextual but not auditory fear memory impairments following 3 months of IL-1β overexpression. On a battery of other behavioral tests, IL-1β overexpression in IL-1β(XAT) mice increased locomotor activity, especially in female mice, and had slight anxiolytic effects. No differences were found in operant conditioning or in basal or stress-induced CORT levels, despite profound hippocampal glial activation. Interestingly, the volume of discrete hippocampal cell layers was reduced after 6 but not 3 months of IL-1β overexpression. Therefore, this animal model provides a novel tool for examining the effects of chronic inflammation on discrete brain regions.