The present study was carried out to investigate the neuroprotective effect of luteolin on amyloid beta (Abeta) (25-35)-induced neurotoxicity using cultured rat cortical neurons. After exposure of primary cultures of rat cortical cells to 10 muM Abeta (25-35) for 48 h, cortical cell cultures exhibited marked apoptotic death. Pretreatment with luteolin (1, 10 microM) significantly protected cortical cell cultures against Abeta (25-35)-induced toxicity. Luteolin (1, 10 microM) showed a concentration-dependent inhibition on 10 muM Abeta (25-35)-induced apoptotic neuronal death, as assessed by MTT assay. Furthermore, luteolin reduced apoptotic characteristics by DAPI staining. For Western blot analysis, the results showed that the protective effect of luteolin on Abeta (25-35)-induced neurotoxicity was mediated by preventing of ERK-p, JNK, JNK-p, P38-p and caspase 3 activations in rat primary cortical cultures. Taken together, the results suggest that luteolin prevents Abeta (25-35)-induced apoptotic neuronal death through inhibiting the protein level of JNK, ERK and p38 MAP kinases and caspase 3 activations.