In our earlier investigations, we have demonstrated the alteration of antioxidant enzymes in adult rat brain exposed to lead. This study was carried out to investigate the effect of lead on inducing apoptosis by choosing poly (ADP-ribose) polymerase (PARP), bcl-2 and caspase-3 expression as marker proteins in the cerebellum, the hippocampus, the brain stem and the frontal cortex. Adult male rats were treated with lead acetate (500ppm) through drinking water for a period of 8 weeks and parallel controls were maintained on sodium acetate. Both control and exposed rats were sacrificed at intervals of 4 and 8 weeks, brains were isolated and different regions namely the cerebellum, the hippocampus, the frontal cortex and the brain stem were separated and processed to investigate PARP, bcl-2 and caspase-3 expression using western blotting. The results suggest that lead induces region-specific response of expression in apoptotic proteins of rat brain showing more effect in hippocampus and cerebellum and less effect in frontal cortex and brain stem and it is tissue specific. However, results appear to conclude that PARP induced expression in hippocampus and cerebellum was more followed by mitochondrial and cytosolic damage.