This review will discuss the recent literature on the molecular mechanism of NF-κB activation, with special focus on IκBα dynamism involved in iNOS- and chemokine-induction in glial cells. NF-κB, a heterotrimer composed of p50, p65 (Rel A) and IκBα, has been shown to be activated by elimination of the regulatory subunit IκBα from the heterotrimer. The elimination of IκBα (formation of active NF-κB, p50.p65) is due to phosplorylation of serines 32 and 36 of IκBα, followed by polyubiquitination and 26S proteasomal degradation of IκBα. Experiments using stable clones of rat C6 glioma cells transfected with dominant negative IκBα (serines 32 and 36 replaced by alanine) suggest that NF-κB activation (phosphorylation of IκBα) is involved in LPS/IFNγ- or IL-1β/IFNγ-induced iNOS expression. Furthermore, the time courses of phosphorylation, ubiquitination of IκBα and proteasome activity after IL-1β treatment also suggest that 26S proteasomal degradation of IκBα is more crucial for chemokine expression in glial cells.