Objective To observe the effect of Ruyanning Decotion combined with exemestane on the expression of JNK/MAPK signaling pathway related protein in MDA-MB-435 breast cancer cells bearing nude mice. To explore the mechanism of Ruyanning Decotion combined with exemestane in the treatment of postmenopausal refractory（HER-2/neu high expression） breast cancer. Methods Created MDA-MB-435 breast cancer cells in tumor bearing nude mouse transplantation model， divided into 4 groups：control group， Ruyanning Decoction group， exemestane group and combination group（Ruyanning Decoction+exemestane）， respectively， once a day by gavage， 21 days after the mice were killed， tumors were. Western blot and RT-PCR were used to detect the expression of JNK/MAPK signaling pathway JNK protein and its downstream related proteins STAT3， Bcl-2， P53 and caspase8 in tumor tissues. Results The inhibition rate of Ruyanning Decoction group， exemestane group and combination group were 37.53%， 60.83%， and 66.09%， respectively. Compared with the control group， Ruyanning Decoction group， exemestane group and combined group of JNK， STAT3 and Bcl-2 protein expression were significantly decreased， with statistical significance（P<0.05）. The expression of JNK protein in the combined group was significantly lower than that in Ruyanning Decoction group and exemestane group（P<0.05）， and the expression of STAT3 protein in Ruyanning Decoction group was significantly lower than that of the exemestane group and the combined group（P<0.05）， and the expression of Bcl-2 protein in the Ruyanning Decoction group， the exemestane group and the combined group， there was no statistical significance between the three groups（P>0.05）. Compared with the control group， Ruyanning Decoction group， exemestane group and combination group of p53 and Caspase8 gene expression were significantly increased， with statistical significance（P<0.05）. The gene expression of p53 and Caspase8 in combined group was significantly higher than that in Ruyanning Decoction group and exemestane group， with statistical significance（P<0.05）. Conclusion Ruyanning Decoction combined with exemestane may have a bidirectional regulation effect on JNK/MAPK signaling pathway. On the one hand， the expression of JNK protein and its downstream protein STAT3 and Bcl-2 can inhibit the proliferation of breast cancer cells. The other side can up regulate the expression of p53 and Caspase8 genes， and play a role in promoting apoptosis of breast cancer cells， and finally play an anti-tumor effect. Combination of Chinese herbal medicine and endocrine therapy will become a new mode of treatment for hormone receptor positive breast cancer in the era of AI+.