Wenshuo Wang,1,* Xiaotian Sun,1,2,* Huili Zhang,3 Cheng Yang,1 Ye Liu,4,5 Wuli Yang,4,5 Changfa Guo,1 Chunsheng Wang1 1Department of Cardiac Surgery, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, 2Department of Cardiothoracic Surgery, Huashan Hospital, Fudan University, 3Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, 4State Key Laboratory of Molecular Engineering of Polymers, 5Department of Macromolecular Science, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Hydrogen sulfide (H2S) functions as a protective gas transmitter in various physiological and pathological processes, but the lack of ideal donors severely hampers the clinical application of H2S. This study aims to construct a controlled release H2S donor and evaluate its protective effect on graft endothelium. Mesoporous silica nanoparticles (MSNs) were synthesized using the sol–gel method and loaded with diallyl trisulfide (DATS), an H2S-releasing agent named DATS-MSN. In vitro experiments showed that DATS-MSN could alleviate endothelial cell inflammation and enhance endothelial cell proliferation and migration. In vivo experiments demonstrated that the apoptosis of graft endothelium was mitigated in the presence of DATS-MSN. Our results indicated that DATS-MSN, releasing H2S in a controlled release fashion, could serve as an ideal H2S donor. Keywords: inflammatory response, rejection, cellular uptake, proliferation, cardiac allograft vasculopathy