Objective:To investigate the protective effects and mechanisms of hawthorn extract against myocardial ischemia-reperfusion (I/R) injury in rats via the HIF-1 signaling pathway.Methods :An ex vivo rat heart I/R model was established. Animals were randomized into five groups: Sham, I/R, low-dose hawthorn flavonoids (HTF-L), high-dose hawthorn flavonoids (HTF-H), and HTF-H combined with the PI3K inhibitor LY294002. Cardiac function (LVSP, LVEDP, ±dp/dt_max), myocardial apoptosis (TUNEL), oxidative stress markers (SOD, MDA), and protein expression of HIF-1α and upstream pathways (PI3K/Akt, MAPK) were assessed after 60 min reperfusion.Results:Compared with Sham, I/R led to significantly impaired cardiac function, increased apoptosis, and oxidative stress. HTF treatment markedly improved cardiac function and suppressed apoptosis and oxidative stress in a dose-dependent manner. Western blot showed that HTF upregulated HIF-1and upstream signaling proteins; PI3K inhibition partially reversed these effects.Conclusion:Hawthorn extract attenuates myocardial I/R injury in rats, likely through activation of the HIF-1 pathway, reduction of apoptosis, and oxidative stress. These findings support the use of hawthorn in cardiovascular protection and provide mechanistic insights.