We examined the modifying effects of freeze-dried whole-leaf Aloe arborescens Miller var. natalensis Berger (designated as ‘ALOE’) onN-ethyl-N’-nitro-N-nitrosoguanidine (ENNG)-induced duodenal tumorigenesis in C57BL/ 6 mice. Experiment 1: Male mice were given ENNG in drinking water for the first 4 weeks, and then 10% ALOE in basal diet for 16 weeks. Experiment 2: Female mice were given ENNG for 5 weeks, and then 5%, 1% or 0.2% ALOE in the diet were given for 15 weeks. In Experiment 1, the tumor incidence and tumor multiplicity (tumors per mouse) of the duodenum in the ENNG + 10% ALOE group were significantly decreased compared with that in the ENNG alone group. Erythrocyte polyamine levels in the ENNG + 10% ALOE group were also significantly decreased. In Experiment 2, the incidence of duodenal tumors in the ENNG + 5% ALOE group were significantly decreased compared with that in the ENNG alone group. These results indicated that ALOE, especially at 10% in the diet, inhibits ENNG-induced duodenal tumorigenesis in mice.