The long term impact of neuroflammation induced by systemic inflammation on astroglial transcription factor nuclear factor (NF)-kappaB activation in the sub-region of hippocampus as well as its' association with the ultra-structural changes in brain cells are yet unknow. In this study, rats received 10 mg/kg of lipopolysaccharide (LPS, ip injection) and NF-kappaBp65 expression on the astroglia as well as the neuronal and astroglial ultra-structural changes and/or death and microvasculature damage were assessed with immunofluorescence and transmission electron microscopy respectively up to 16 days after treatment. The results showed that in the CA1 and CA3 region of the hippocampus, the fluorescence intensity of NF-kappaBp65 was increased from day 1 after LPS injection, reaching a peak at day 3, and stayed at higher level when compared to the control up to 16 days after LPS treatment (P<0.05). Electron microscopy studies revealed sustainable substructural alterations, injury or even death of astrocytes, neurons and capillaries even after 16 days post LPS injection. Our study demonstrated that long-term sustainable activation of astroglial NF-kappaB following systemic inflammation was associated with brain cell and microvasculature injury in the sub-region of the hippocampus which ultimately likely results in brain functional impairment.