Abstract: Objective To investigate the effect of chronic emotional stimulation induced by empty bottle stimulation on CXCL12/ CXCR4-mediated inflammatory response in rats with acute myocardial infarction (AMI). Methods Rat models of anxiety were established by a 21-day stimulation with uncertain empty bottle drinking water, and myocardial infarction was induced by ligating the left anterior descending branch of the coronary artery; compound models were established by performing myocardial infarction operation on the 15th day of anxiety modeling. The rats were randomly divided into 4 groups: shamoperated group (n=6), myocardial infarction group (n=6), compound model group (with myocardial infarcted and anxiety; n= 6), and inhibitor group (compound models treated daily with 1 mg/kg AMD3100 for 6 days; n=7). Echocardiography was used to examine the LVEF and LVFS to evaluate the cardiac function of the rats. Elevated maze test and open field test were used to evaluate the behaviors of the rats. The expressions of CXCL12, CXCR4, IL-1β, IL-18 and neutrophil active protease (NE) in the myocardial tissues and blood samples were detected with ELISA and immunohistochemistry. Results The LVEF and LVFS were lower in the compound model group than in the sham group and myocardial infarction group (P<0.05), and were higher in inhibitor group than in the compound model group (P<0.05). LVID;d and LVID;s were lower in the inhibitor group than in the compound model group (P<0.05). Compared to those in the sham group and myocardial infarction group, the rats in the compound model group more obviously preferred to stay in the closed arm (P<0.05) in EPM; the rats in the inhibitor group had more times of entering and staying in the open arm than the compound model rats (P<0.05); the horizontal and vertical movements were less in the compound model rats than in those in the sham group and the myocardial infarction group (P<0.05) in OFT, and the vertical movement of the rats in inhibitor group was higher than those in the compound model group (P< 0.05). The expression of CXCR4 in the marginal zone of myocardial infarction was significantly higher in the compound model group than in the sham-operated group, myocardial infarction group and inhibitor group (P<0.05). The expressions of IL-1β, IL-18 and NE in the inhibitor group were significantly lower than those in the compound model group (P<0.05). Compared with at in the sham-operated group, the number of Nissl bodies in the compound model group decreased significantly (P< 0.01). Conclusion Chronic emotional stress induced by empty bottle stimulation can lead to dysfunction of the CXCL12/CXCR4 axis, which causes inflammatory cascade after myocardial infarction to worsen myocardial cell necrosis, cardiac function and hippocampal neuronal damage after the infarction.