Genistein (GEN), a major soybean isoflavone (SIF), might possess neuroprotective properties through its antiinflammatory activity. We hypothesized that GEN could prevent the inflammatory damage detected in C6 cells induced by b-amyloid peptides [25][26][27][28][29][30][31][32][33][34][35]. Accordingly, we evaluated the inflammatory damage induced by Ab25-35 and the protective effect of GEN against Ab25-35 in C6 cells. In our study, the C6 glial cells (rats glioma cell lines) were preincubated with or without GEN for 2 h following incubation with Ab25-35 for another 24 h. Then, methylthiazolyl tetrazolium (MTT) assay was used to assess the cell viability. Immunofluorescence staining was used to identify the C6 cells. Inflammatory factors tumor necrosis factor (TNF)-a and interleukin (IL)-1b were analyzed by using enzyme-linked immunosorbent assay (ELISA). Western blot analysis and reverse transcription-polymerase chain reaction analysis were performed to assess the expression of Toll-like receptors 4 (TLR4), inhibitor of kappaB-alpha (IjB-a). The current results showed that GEN could alleviate Ab25-35-induced cell apoptosis and prevent Ab25-35-induced TNF-a and IL-1b release from C6 cells. In addition, GEN prevented Ab25-35-induced upregulation of the gene and protein expression of TLR4, and GEN significantly upregulated the expression of IjB-a in C6 cells damaged by Ab25-35. These results suggest that GEN can alleviate the inflammatory stress caused by Ab25-35 treatment, which might be associated with the neuroprotective effect of GEN regulating the TLR4/NFjB signaling pathway.