Abstract: Objective: To investigate the effect of estrogen and estrogen antagonist on the upstream kinase MEK-2and the downstream kinase p-ERK in the MAPK signal transduction pathway in breast cancer. Methods: Estrogen (E2)and estrogen antagonist (TAM) were given to induce breast cancer tissue formation in BCML-TA299 mice after in situtransplantation, and then the expression of ERβ, MEK-2 and p-ERK was detected by pathomorphology and immunohis-tochemistry. Results: E2 promoted cell proliferation. There was more karyokinesis and redundant blood vessels in tumortissues, especially those found in the lung. Many tumor emboli were seen in the heart chambers. TAM suppressed cellproliferation. Cancer cells treated with TAM were seriously damaged and displayed nuclear fragmentation, apoptotic bod-ies, focal degeneration and necrotic regions. Simultaneously, the expression of ERβ, MEK-2 and p-ERK were downregu-lated. Combined application of TAM and CTX achieved better results (F=211.88, F=179.08, F=156.44, P<0.05). Conclusion: There is a close relationship between ERβ, MEK-2 and p-ERK. These signaling pathway proteins act synergisticallyin breast cancer development.