Objective To explore the mechanism of Huoxue Xiaoyi Recipe on endometrial receptivity and CXCL12/CXCR4 signaling pathway in rats with endometriosis. Methods The rats were divided into sham operation group, model group (endometriosis rat model group)，traditional Chinese medicine group (endometriosis rat model group was given Huoxue Xiaoyi prescription intervention treatment group) and western medicine group (endometriosis rat model group was given leproteroline acetate intervention group) according to digital random method, with 10 rats in each group. The levels of E2 and P in serum were detected by ELISA, the histopathological changes of endometrium were detected by HE staining, and the levels of LIF and P in endometrium were detected by ELISA αvβ3 The protein expressions of cxcl3, LIF, αvβ3. CXCL12 and CXCR4 protein expression were detected by Western blot. CXCL12 and CXCR4 mRNA expression were detected by RT-PCR. Results The levels of E2 and P in the model group were significantly lower than those in the sham operation group (P<0.05). Compared with the model group, the levels of E2 and P in western medicine group and traditional Chinese medicine group were increased in varying degrees, and the levels of E2 and P in traditional Chinese medicine group were significantly increased (P<0.05). In the model group, the expression of LIF and α v β 3 protein expression was significantly lower than that in sham operation group (P<0.05). After the intervention, LIF in the western medicine group and the traditional Chinese medicine group α v β 3 protein expression increased significantly, and Chinese medicine group increased more significantly (P<0.05). The protein and relative expression of CXCL12 and CXCR4 in endometrium of model group were significantly higher than those of sham operation group (P<0.05). After intervention, the protein and relative expression of CXCL12 and CXCR4 in endometrium of Western medicine group and traditional Chinese medicine group were significantly lower than those of model group, and the protein and relative expression of CXCL12 and CXCR4 in traditional Chinese medicine group were significantly lower than those of Western medicine group (P<0.05). Conclusion Huoxue Xiaoyi decoction can improve the endometrial receptivity of Endometriosis Rats, and has obvious inhibitory effect on the expression of CXCL12 and CXCR4 in Endometriosis Rats.