This study is to investigate the protective effect of longistyline A against corticosterone-induced neurotoxicity in PC12 cells.  While PC12 cells were exposed to 100 μmol·L⁻¹ corticosterone for 48 h, cell survival rate was reduced and lactate dehydrogenase (LDH) release increased.  In parallel, corticosterone caused significant elevations of DNA fragmentation, Ca²⁺_i and caspase-3 activity.  However, when the PC12 cells were incubated with longistyline A (4.0, 8.0 and 16.0 μmol?L⁻¹) in the presence of 100 μmol·L⁻¹ corticosterone for 48 h, the effects were evidently alleviated, but dose-dependent manner was not obvious.  In summary, longistyline A could generate a neuroprotective effect against corticosterone-induced neurotoxicity in PC12 cells possibly by decreasing Ca²⁺_i and caspase-3 activity.