Abstract: The protective effect and mechanism of Oroxylin A, a naturally occurring compound in Scutellaria baicalensis Georgi, was investigated in this study. Isoproterenol administration to rats triggered classic cardiac failure, as demonstrated by objective parameters of cardiac dysfunction. Intragastric administration of oroxylin A at the dose of 25, 50 and 100 mg/(kg·d)significantly improved deranged cardiac parameters in the isoproterenol-induced heart failure model in a dose-dependent manner. At the same time, oroxylin A markedly ameliorated cardiac histological changes and down-regulated serum levels of various neuroendocrine factors including norepinephrine, aldosterone, brain natriuretic peptide, endothelin 1, angiotensin II and so on. Mechanistically, augmenting autophagy of myocardial cells via the inhibition of AKT1-RPS6KB1 signaling contributed to the improvement of isoproterenol-induced rat heart failure by oroxylin A. Taken together, these results suggest that oroxylin A ameliorates heart failure through promoting autophagy in myocardial cells.