Induction of apoptosis is one of the most active strategies in cancer chemoprevention and the ability of medicinal plants in this regard has attracted major research interest. The present study was designed to investigate the apoptosis inducing capacity of an ethanolic neem leaf extract (ENLE) during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis using the apoptosis-associated proteins Bcl-2, Bim, caspase 8 and caspase 3 as markers. Topical application of DMBA to the hamster cheek pouch for 14 weeks resulted in well developed squamous cell carcinomas associated with increased expression of Bcl-2 and decreased expression of Bim, caspase 8 and caspase 3. Administration of ENLE inhibited DMBA-induced hamster buccal pouch (HBP) carcinogenesis, as revealed by the absence of neoplasms, with induction of Bim and caspases 8 and 3 and inhibition of Bcl-2 expression. Our results suggest that the chemopreventive effects of ENLE may be mediated by induction of apoptosis.