Abstract: Objective: To observe the effect of Sulindac on changes of the apoptosis regulating genes in different stages of the tumor formation, and probe the possible anticarcinogenic molecular mechanism of sulindac. Methods: The expressions of p53, Bcl-2 and Bax on different stages of tumor formation in mice models of 1, 2-dimethylhydrazin (DMH)-induced colon carcinogenesis were deter-mined by immunohistochemical staining. Results: During the formation of colorectal tumorigenesis, a-long with the aggravation of atypical hyperplasia, the density of p53 and Bax gradually rose (P<0.01),but Bcl-2 and Bcl-2/Bax ratio decreased after reached maximum value at the third or the second stage.At the end of the experiment, the density of p53, Bcl-2 and Bcl- 2/Bax ratio were higher in prevention group than that in model group (all P<0.01 except p53); but in the treatment group, only Bax was signif-icantly lower than that in the model group (P<0.01). Conclusion: During the course of colon carcino-genesis, sulindac induces the apoptosis of colon epithelial cells by down-regulating the expression ofmutant p53 and Bcl-2 to inhibit the development of colon cancer.