AIM: To investigate effect of sodium ferulate on A?25-35-mediated signaling pathway. METHODS: The isolated peritoneal macrophages from mice were cultured. p38 MAPK protein kinase in nuclear extracts was analyzed by Western blotting. The concentration of TNF-? and NO in supernatant were measured by ELISA and Griess reaction technique. The expression of iNOS protein was detected by immunochemical technique. RESULTS: A?25-35 significantly increased the concentrations of TNF-? and NO in supernatant, expression of iNOS in macrophages and p38 MAPK protein kinase in nuclear extracts, which were blocked by sodium ferulate. CONCLUSION: Sodium ferulate inhibits p38 MAPK activation triggered by A?25-35.