This study was aimed to investigate the nitric oxide (NO)-induced cytotoxic mechanism in PC12 cells. Sodium nitroprusside (SNP), an NO donor, decreased the viability of PC12 cells in dose- and time- dependent manners. SNP enhanced the production of reactive oxygen species (ROS), and gave rise to apoptotic morphological changes including cell shrinkage, chromatin condensation, and DNA fragmentation. Expression of Bax was not affected, whereas Bcl-2 was downregulated in SNP-treated PC12 cells. SNP augmented the release of cytochrome c from mitochondria into cytosol and enhanced caspase ⁣8, ⁣9, and ⁣3 activities. SNP upregulated both Fas and Fas-L, which are known to be components of death receptor assembly. These results suggest that NO induces apoptosis of PC12 cells through both mitochondria- and death receptor-mediated pathways mediated by ROS and Bcl-2 family.