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Objective To investigate the effect of Yangxin Shengmai (Heart-nourishing Pulse-engendering) Granule (YXSM Granule) on rats with coronary heart disease complicated with anxiety and depression through BDNF/TrKB pathway. Methods 124 SD rats were randomly divided into the blank group (n =14) and the model group (n =110). Except for the blank group, the depression model was established with Chronic Unpredictable Mild Stress (CUMS) for 28 days. On the 15th day, the myocardial infarction reperfusion model was established by ligating the left anterior descending coronary artery. Among the rat models, 14 rats were operated but not ligated, and they were set as the sham operation group; the others were randomly divided into model group and low-, medium- and high-dose (2.1,4.2,8.4 g/kg) YXSM Granule groups and 0.29 g/ kg Compound Danshen tablet + Fluoxetine (CDST+Flu) group. After intragastric administration for 2 weeks, the rats in each group undergone behavioral tests. The myocardial injury, left ventricle diameter (LVD) and left ventricular wall thickness (LVWT) were observed by HE staining, the protein expression levels of BDNF, TrKB and CD34 in myocardial tissue were detected by immunohistochemistry, and the protein expression levels of BDNF, TrKB and p-TrKB in hippocampus were detected by Western blotting. Results Compared with the sham group, the frequency of entering the central area of the open field and the total time spent and total distance travelled in the movement track in the model group were significantly reduced (P < 0.01), and the frequency and proportion of time spent in the open arm of the elevated cross maze were significantly reduced. Compared with the model group, the frequency of entering the central area of the open field and the total time spent and distance travelled in the movement track in all YXSM Granule groups and CDST+ Flu group were significantly increased (P<0.01), and the frequency and proportion of time spent in the open arm of the elevated cross maze were significantly increased, but with no significant difference. Compared with the sham operation group, in the model group, the degree of myocardial injury and LVD were significantly increased (P<0. 01), the LVWT and the protein expression levels of BDNF, TrKB and CD34 in myocardial tissue and BDNF and p-trkb/TrKB in hippocampus decreased significantly (P<0.05, P<0.01). Compared with the model group, the degree of myocardial injury was significantly improved, the LVD was significantly reduced (P<0.01), the LVWT and the protein expression levels of BDNF, TrKB and CD34 in myocardial tissue and BDNF and p-TrKB/ TrKB in hippocampus were significantly increased (P<0.05, P<0.01) in all the other groups. Conclusion YXSM Granule seems to improve the cardiac function and alleviate depressive symptoms in rats with coronary heart disease with anxiety and depression, which may play a cardioprotective and antidepressant role by activating BDNF/TrKB signal pathway. [ABSTRACT FROM AUTHOR]