To investigate the potential effects of Eryngium foetidum Linn. leaves (EF) in colitis-induced colorectal carcinogenesis in mice by azoxymethane (AOM) and dextran sulfate sodium (DSS), 39 ICR male mice were studied and divided into 6 groups. The mice were received a modified AIN-76 diet in Group 1, whereas Group 2 was given an AOM, DSS, and AIN-76 diet. Groups 3 and 4 were fed with 0.8% and 3.2% freeze-dried EF with AIN-76 diets, for 5 wk. Groups 5 and 6 were fed with 0.8% and 3.2% EF diets for 5 wk during AOM/DSS administration. The mice were necropsied at Week 20 and their colons were collected. The results indicated that the incidences of tumors in Groups 2, 5, and 6 was 100%, 75%, and 88%, with multiplicities (mean ±SE) of 3.75 ±0.92, 2.38 ± 0.96 and 4.25 ± 0.79, respectively. Interestingly, there was a significant difference in COX-2 expression in mice received 3.2% EF in their diet, but the proliferative cell nuclear antigen index and iNOS protein expression were not significantly different. We concluded that EF at a dose level of 3.2% in their diet had a preventive effect on colorectal carcinogenesis via the proinflammatory cytokine, COX-2.