Objective To investigate chemopreventive mechanism of metformin or celecoxib on chemically induced colorectal aberrant crypt foci in mice. Methods Forty five 6-week-old BALB/c female mice were randomly divided into 3 groups: control group, metformin group and celecoxib group. After one week adaptation, the mice were injected intraperitoneally with 10 mg/kg of AOM, once a week for two weeks. The mice in control group, metformin group and celecoxib group were treated with saline, metformin and celecoxib by gavage, respectively. The changes in body weight were monitored weekly in mice. After 6 weeks, mice were sacrificed and the colorectal tissues were separated. Proliferation of lesions tissue was detected by proliferating cell nuclear antigen(PCNA)labeling indices, and apoptosis was detected by transferase deoxynucleotidyl uridine end labeling(TUNEL)staining. Moreover, to assess the state of mice insulin resistance, the fasting plasma glucose and insulin in mice were detected. Results The proliferation index(PI)of metformin group and celecoxib group were respectively(27.30±1.49)and(37.20±2.10),which was lower than that of the control group(56.20±1.93), (P<0.05). Metformin had stronger inhibitory effect than celecoxib on cell proliferation(P<0.05). The apoptosis index(AI)in metformin group and celecoxib group were(7.70±1.25)and(7.00±1.05)respectively, which was higher than that in the control group(5.10±1.37), (P<0.05). No significant difference in fasting plasma glucose and insulin resistance index of mice was found between control group, metformin group and celecoxib group(P>0.05). Conclusion We confirm that metformin and celecoxib may play a preventive role for colorectal cancer. The mechanism may be related to the inhibition of cell proliferation and promoting of apoptosis. Moreover, the effect of metformin is better than celecoxib.