We report the chemopreventive activity of Acacia nilotica (Linn.) gum, flower and leaf aqueous extracts, on 7,12–dimethylbenz(a)anthracene (DMBA) induced skin papillomagenesis in male Swiss albino mice. Animals were dividedinto following groups: Group I (Controls) given DMBA and croton oil, with no extract ; Group II (treatment) animalstreated with Acacia nilotica gum (Group II-a) (800 mg/kg body weight), flowers (Group II-b) (800 mg/kg bodyweight), or leaves (Group II-c) (800 mg/kg body weight) during the peri- and post initiation periods of DMBA andcroton oil application. A significant reduction in the values of tumor burden, tumor incidence and cumulative numberof papillomas was observed in mice treated by oral gavage with the Acacia nilotica gum, flower and leaf extracts ascompared with the control group. The latency period in treatment Group-II (b) and Group-II (c) was significantlyincreased as compared with the control group. A significant reduction in the frequency of micronuclei was alsoobserved in mice treated by oral gavage with the aqueous extracts, along with significant decrease in total chromosomalaberrations in the form of chromatid breaks, chromosome breaks, centric rings, dicentrics, acentric fragments andexchange. Treatment with Acacia nilotica flower (Group II-B) and leaf (Group II-C) aqueous extracts by oral gavagefor 15 days resulted in a highly significant decrease in the lipid peroxidation (LPO) level in the liver, but this was lessevident with the gum (Group II-A) . Conversely, reduced glutathione (GSH) content was observed to be significantlyelevated as compared with the control group with leaves (Group II-C) and flowers (Group II-B). The chemopreventiveand antimutagenic activity of the leaf extract of Acacia nilotica was most significant followed by the flower extractand then by gum.