【Abstract】 Objective To evaluate the characteristics of a rat model of heart failure with preserved ejection fraction (HFpEF) induced by combined factors and to investigate the correlation of myocardial strain parameters with myocardial hypertrophy and fibrosis. Methods Eight WKY rats and eight spontaneously hypertensive rats (SHR) served as control groups and were given normal feed until the end of the experiment. Thirty two SHR rats were equally divided into SHR+S, SHR+F, SHR+SF, and SHR+ combined groups. They were fed with high salt feed, high fat feed, high salt-fat feed, and high salt-fat-sugar feed in combination with streptozotocin intraperitoneally for 30 weeks, respectively. After modeling, heart weight/body weight (HW/BW), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured; Echocardiography was performed to measure left ventricular (LV) end-diastolic internal diameter (LVIDd), LV anterior wall thickness (LVAWd), LV posterior wall thickness (LVPWd), LV ejection fraction (LVEF), isovolumetric diastolic time (IVRT), and peak early diastolic passive filling velocity (E) / early diastolic mitral annular velocity (e'); Speckle tracking echocardiography was conducted to determine global longitudinal strain (GLS) and strain rate (GLSr), global radial strain (GRS) and strain rate (GRSr), as well as global circumferential strain (GCS) and strain rate (GCSr); Serum is used to detect triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), glucose (GLU), and glycated serum protein (GSP); ELISA was used to examine serum B-type brain natriuretic peptide (BNP), angiotensin II (AngII),and Galectin-3 (Gal-3); Myocardium was subjected to HE and Masson staining for cardiomyocyte and myocardial fibrosis, and cardiomyocyte cross-sectional area (CSA) and collagen volume fraction (CVF) were calculated; In addition, the correlation of myocardial strain parameters with CSA and CVF was analyzed. Results Compared with the control group, in the model groups, especially in the SHR+Combined group, HW/BW, SBP, DBP, serum indexes (TC, TG, LDL-C, GLU, GSP, BNP, AngII, and Gal-3), and echocardiographic parameters (LVIDd, LVAWd, LVPWd, IVRT, and E/e') were significantly up-regulated; Absolute values of speckle-tracking echocardiographic parameters (GLS, GLSr, GRS, GRSr, GCS, and GCSr) were decreased considerably; HE and Masson staining of myocardial tissues suggested marked cardiomyocyte hypertrophy and fibrosis, and there were significant increases in CSA and CVF (P<0.01 or 0.05). Correlation analysis showed that GLSr, GCS, and GCSr were strongly linked to CSA; GLS, GLSr, and GCSr were strongly linked to CVF (P<0.01). Conclusions A rat model of HFpEF induced by hypertension and dysregulation of glucolipid metabolism replicated the basic characteristics of HFpEF in terms of etiology, clinical features, and myocardial pathologic changes and might be a reliable animal model of metabolic syndrome-related HFpEF. Moreover, myocardial strain indices are closely related to myocardial hypertrophy and fibrosis and might indirectly reflect subtle myocardial lesions and dysfunction.