In order to investigate the inhibitory effect of tamoxifen (TAM) on breast cancer risk induced by exogenous estrogen, female rats were randomly allocated into three groups, namely DES (diethylstilbestrol) group, DES + TAM group and blank control group. We found that in DES + TAM group the levels of estradiol (62.14 pg/ml) and progesteron (15.02 ng/ml) in serum were obviously higher than those in DES group (52.69 pg/ml, 10.38 ng/ml) individually (P < 0.05, P < 0.01), the incidence (28.57%) of mammary hyperplasia was significantly lower than that in DES group (73.33%) (P < 0.025), the degree of hyperplasia markedly slighter than that in DES group (P < 0.025), and the AgNOR count (1.93%), DNA content (80.24%) and ER positive rate (36.46%) were obviously lower than those in DES group (2.43%, 95.60%, 71.71%) individually. The results indicated that TAM could increase the levels of estradiol and progesterone in serum, also could decrease the ER contents, AgNOR counts and DNA contents in mammary epithelium. It suggested that the TAM could interfere the effect on the breast carcinogenesis induced by exogenous estrogen.