Abstract: The aim of the present study was directed to investigate the effect of rosmarinic acid (RA) as a chemopreventive modality on experimentally induced hamster buccal pouch (HBP) carcinogenesis. Material and methods: Forty Syrian male hamsters five weeks old, weighing 80-120g, were divided into four groups of ten animals in each as follows, GI: Topical application of liquid paraffin alone (three times a week for 14 weeks), GII: Topical application of 7, 12 dimethyl benz[a]anthracene (DMBA) alone (0.5% in liquid paraffin, three times a week for 14 weeks), GIII: Topical application of DMBA (0.5% in liquid paraffin, three times a week for 14 weeks) + Oral administration of RA (100mg/kg b.w in 1ml distilled water by oral gavage, three times a week for 14 weeks on alternate days of DMBA application), GIV : Oral administration of RA alone (100mg/kg b.w in 1ml distilled water by oral gavage, three times a week for 14 weeks). Results: Gross observation and histopathological findings revealed a-GI: normal stratified squamous epithelium b- GII: well and moderately differentiated SCC c-: GIII: revealed considerably reversed tumor incidence d: GIV: normal similar to GI. Immunohistochemical results revealed, oral administration of RA to DMBA treated hamsters restored the normal expression of bcl-2 and Bax indicating that RA may have chemopreventive mechanism and/or pro-apoptotic effects. Conclusion: RA may act through various mechanisms, such as exerting anti-inflammatory, antioxidant effects as well as inhibiting cell proliferation, migration, and selectively inducing cancer cells apoptosis.