Heart failure with preserved ejection fraction HFpEF continues to increase and little is known about its pathophysiology. About 23 of patients are women and risk factors include aging, hypertension and metabolic syndrome. A feature of the disease is cardiac fibrosis. Currently, no drugs target HFpEF and the development of animal models can assist in therapy evaluation. We developed a female rat model of aging, estrogen depletion and metabolic syndrome to evaluate the role of these factors in altering cardiac structurefunction. Aged female Fischer F344 rats were allocated into an aging group, aging ovariectomy and aging ovariectomy 10 fructose in drinking water. At 22 months of age, animals were anesthetized and left ventricular LV function was evaluated. Histological measures were also obtained. Intraventricular pressure-volume loop analysis evidenced significant decreases in stroke work cardiac output and increases in myocardial stiffness with ovariectomy. Histological analysis indicated increasing levels of inflammatory infiltration, perivascular and interstitial fibrosis with ovariectomy and with fructose supplementation. In conclusion, with aging, estrogen deprivation, markedly deteriorates myocardial microstructure which may facilitate the loss ofdiastolic and systolic function. This model may serve to understand the role that aging and menopausemay have in the development of HFpEF.