Abstract: OBJECTIVE: To observe the effect of Rupifang Extract in external use on expression of proto-oncogenes her2 and tumor suppression genes p16 in rat breast tissues of mammary hyperplasia model. To explore the mechanisms of Rupifang Extract in external use for preventing and treating mammary hyperplasia. METHODS: Thirty virginal female Wistar rats wererandomized into 5 groups, 6 in each, A: blank controlgroup; B: model group; C: the low dose groupof Rupifang; D: the middle dose group of Rupifang;and E: The high dose group of Rupifang. The ammaryhyperplasia rat models were produced by injectingestradiol benzoate and progesterone and irritatingby tail nipping. Drug intervention was alsolaunched during the model formation. After 30days, the expression of her2 and p16 in breast tissuesof rats in each group were detected by the SPimmunohistochemical method.RESULTS: Compared with Blank control group, theexpression of her2 in breast tissues in Model groupwas higher, and the expression of p16 was lower(P<0.05 or P<0.01). After intervention with RupifangExtract, compared with Model group, the expressionof her2 in breast tissues in Rupifanggroups was lower, and the expression of p16 higher(P<0.05 or P<0.01).CONCLUSION: The mechanisms of Rupifang Extractin external application for preventing andtreating mammary hyperplasia may be reducingthe expression of proto-oncogenes her2 and increasingthe expression of tumor suppressiongenes p16.