The present study explored the effect of curcumin against amyloid β (Aβ)-induced toxicity on cultured rat primary prefrontal cortical neurons. The results showed that administration of 10μM of curcumin induced significantly protection against 20μM of Aβ_25–35-induced toxicity on the cultured rat primary prefrontal cortical neurons tested by MTT and TUNEL assays. We further examined the involvements of the apoptotic or anti-apoptotic proteins in curcumin protection against Aβ_25–35-induced cytotoxicity on cultured neurons and found that the content of apoptotic protein caspase-3 was increased and the content of anti-apoptotic factor Bcl₂ was decreased significantly after Aβ_25–35 treatments, while administration of curcumin significantly inhibited the Aβ_25–35-induced increases in the content of caspase-3 and inhibited the Aβ_25–35-induced decreases in the content of Bcl₂ tested by Western blot. The results suggest that curcumin protects cultured rat primary prefrontal cortical neurons against Aβ-induced cytotoxicity, and both Bcl₂ and caspase-3 are involved in the curcumin-induced protective effects.