LPS, a bacterial endotoxin, is known to affect various functions of the central nervous system, including stimulation of the hypothalamo-pituitary-adorenal axis. LPS also produces deficits in learning and memory. We have previously reported that LPS decreased immunoreactivity of c-Fos in the dentate gyrus (DG) of hippocampus. In the present study, we examined whether LPS treatment may differentially influence c-Fos expression in subregions of the DG. Ovariectomized rats were treated with an intravenous (iv) injection of LPS (40 μg/kg) or saline. Two hours or six hours after the injection, the brains were fixed and immunohistochemistry against c-Fos was performed. In the whole DG, LPS treatment significantly decreased the number of c-Fos immunoreactive cells as we reported previously. In the infrapyramidal blade of granule cell layer, c-Fos expression was dramatically decreased by LPS treatment. LPS also decreased c-Fos immunoreactivity in the suprapyramidal blade of the DG. However LPS did not affect c-Fos immunoreactive cell number in the polymorphic cell layer of the DG. Pretreatment with metyrapone (75 mg/kg), an inhibitor of glucocorticoid synthesis, had no effect on LPS induced decline in c-Fos expression in the DG and subregional specificity. These results show that LPS treatment selectively decreases c-Fos expression in the granule cell layer of the DG, especially in the infrapyramidal blade of the DG, and glucocorticoid has no effect on c-Fos expression pattern in these areas. [J Physiol Sci. 2008;58 Suppl:S218]