【Abstract】 Objective To investigate the impact and molecular mechanism of taxifolin (TAX) on myocardial hypertrophy in spontaneously hypertensive rats (SHR). Methods Twenty-four SHRs were separated into SHR control group (SHR group), TAX group (20 mg/kg), and TAX PERK activator CCT020312 (CCT) group (20 mg/kg TAX 2 mg/kg CCT), 8 per group; another 8 normal blood pressure Wistar-Kyoto (WKY) rats were regarded as the normal control group (WKY group), and all were given corresponding drugs for 8 weeks of continuous intervention. During the experiment, the changes in blood pressure of the rats were observed, and after the intervention, the thickness of the diastolic ventricular septum (IVSd), the thickness of the systolic ventricular septum (IVSs), and the left ventricular ejection fraction (LVEF) were detected by echocardiography to determine the degree of myocardial hypertrophy and cardiac function, then the cardiac index and left ventricular index were calculated, hematoxylin-eosin (HE) staining, wheat germ agglutinin (WGA) staining and Masson staining were performed to evaluate the pathological changes of myocardial tissue, real-time quantitative PCR (qRT-PCR) was performed to detect the expressions of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), type I collagen α1 chain (COL1A1) and type III collagen α1 chain (COL3A1) mRNA in myocardial tissues, Western blot was performed to detect the expressions of protein kinase R-like endoplasmic reticulum kinase (PERK)-activator of transcription 4 (ATF4) pathway-related proteins in cardiac muscle. Results After the intervention, compared with the WKY group, the systolic blood pressure (SBP), diastolic blood pressure (DBP), IVSd, IVSs, cardiac index, left ventricular index, myocardial cell cross-sectional area, collagen volume fraction (CVF), myocardial tissue ANP, BNP, COL1A1 and COL3A1 mRNA expressions, glucose-regulated protein 78 (GRP78), ATF4, C/EBP homologous protein (CHOP) protein levels and p-PERK/PERK ratio in the SHR group increased (all P<0.05), LVEF decreased (P<0.05); compared with SHR group, the SBP, DBP, IVSd, IVSs, cardiac index, left ventricular index, myocardial cell cross-sectional area, CVF, myocardial tissue ANP, BNP, COL1A1 and COL3A1 mRNA expressions, GRP78, ATF4, CHOP protein levels and p-PERK/PERK ratio in TAX group decreased (all P<0.05), LVEF increased (P<0.05); CCT020312 partially reversed the protective effects of TAX on cardiac function and cardiac hypertrophy. Conclusion TAX can improve hypertensive myocardial hypertrophy by inhibiting endoplasmic reticulum stress (ERS), and its mechanism may be related to inhibiting PERK-ATF4 pathway.