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Abstract Cardiac transplantation has been limited by the inability to long preserve donor hearts safely. Hydrogen sulfide (H 2 S) has been recognized as an important gasotransmitter exerting potent cardioprotection from ischemia/reperfusion injury (I/R). Herein we investigated the cardioprotective effects of a novel long-term and slow-releasing H 2 S system, namely DATS-MSN, in heart preservation solution using a heart transplantation models. The release of H 2 S from DATS-MSN was slow and continuous in the University of Wisconsin solution (UW), correspondingly, DATS-MSN application demonstrated superior cardioprotective effects over the control and traditional H 2 S donors after 6 h heart preservation and 1 h reperfusion, associated with greater allograft performance including left ventricular developed pressure (LVDP) and dP/dt max , reduced plasmic CK-MB and troponin I levels, inhibited myocardial inflammation, increased antioxidant enzyme activities, preserved mitochondria structure and function, and decreased cardiomyocyte apoptosis index. Also, DATS-MSN application presented significant superiority in long-term allografts survival and function after 8 weeks of transplantation. In the in vitro experiments, cardiomyocytes injury from hypoxia was found to be relived with the treatment of DATS-MSN by anti-inflammatory effects via TLR4/NLRP3 pathway. The present work provides a long-term releasing H 2 S donor compatibly applied in the donor heart preservation, and preliminary explores its underlying mechanisms. Highlights • The present work provides a useful platform in H 2 S study especially in organ preservation field. • It offers an insight into how the H 2 S release patterns from different H 2 S donors affect their physiological functionality. [ABSTRACT FROM AUTHOR]