Aim: To observe whether an amyloid β (Aβ)-induced increase in interleukin (IL)1 β was accompanied by an increase in the p38 mitogen-activated protein kinase (MAPK) pathway and a decrease in the cell survival pathway, and whether sodium ferulate (SF) treatment was effective in preventing these Aβ-induced changes.Methods: Rats were injected intracerebroventricularly with Aβ25-35. Seven days after injection, immunohistochemical techniques for glial fibrillary acidic protein (GFAP) were used to determine the astrocyte infiltration and activation in hippocampal CA1 areas. The expression of IL-1 β, extracellular signal-regulated kinase (ERK), p38 MAPK, Akt/protein kinase B (PKB), Fas ligand and caspase-3 were determined by Weste blotting. The caspase-3 activity was measured by cleavage of the caspase-3 substrate (Ac-DEVD-pNA). Reverse transcriptionpolymerase chain reaction was used to analyze the changes in IL- 1 βmRNA levels.Results:Intracerebroventricular injection of Aβ25-35 elicited astrocyte activation and infiltration and caused a strong inflammatory reaction characterized by increased IL-1 β production and elevated levels of IL-1 β mRNA. Increased IL-1 β synthesis was accompanied by increased activation of p38 MAPK and downregulation of phospho-ERK and phospho-Akt/PKB in hippocampal CA regions prepared from Aβ-treated rats, leading to cell death as assessed by activation of caspase-3. SF significantly prevented Aβ-induced increases in IL-1 β and p38 MAPK activation and also Aβ-induced changes in phospho-ERK and phospho-Akt/PKB expression levels. Conclusion: SF prevents Aβ-induced neurotoxicity through suppression of p38 MAPK activation and upregulation of phospho-ERK and phospho-Akt/PKB expression.survival signals ERK and Akt/PKB may contribute to the demise of the cells. These are significantly abrogated by SF treatment, which also attenuates Aβ-induced increase in caspase-3 activity and FasL expression.