Nitric oxide (NO) can be either neuroprotective or neurotoxic, depending on the cell type from which it is released and the length and severity of the ischemic insult. In the present study, we investigated the neuroprotective effect of Seongpungtang, a Oriental traditional medicine, on ischemic brain insult by C(6) glial cells and microglia produced NO. O production was induced by lipopolysaccharide (LPS) only or LPS combined with phorbol-12-myristate-13-acetate (PMA) in C(6) glial cell and microglia, and we observed the suppressive effect of Seongpungtang on NO production increased by LPS only or LPS combined with PMA. The cells treated with the water extracts of Seongpungtang at 2 mg/ml does not change the viability. And the water extracts of Seongpungtang significantly suppress the NO production induced by LPS or LPS combined PMA in C(6) glial cells and microglia. To validate the neuroprotective effect of Seongpungtang by suppression of NO production, the microglial cells were treated with NF-kB inhibitor pyrrolidine dithiocarbamate (PDTC), and it is completely decreased the NO production induced by LPS combined with PMA. Moreover, the water extracts of Seongpungtang suppress morphological degeneration by LPS combined with PMA in C(6) glial cell and microglia. These results suggest that the protective effects of the water extracts of Seongpungtang against ischemic brain damages may be mediated by regulation of iNOS during ischemic condition.