Background Endogenous mediators of remote ischemic conditioning (RIPC) have been drawn researchers’ attention as the most important contributors. Objective This paper reviews the relative researches of endogenous mediators involved in the RIPC. Content Various animal studies have proved that the RIPC induced whole blood or coronary effluent from one organ can confer protective potential during ischemic/reperfusion injury(I/RI) in another heart. However, the exact mechanism remans unknown. The researchers have summerized the animal studies regarding the introduction, identification, characteristics and intracellular signal mechanisms of endogenous mediators. Meanwhile, some related evidences in human have also been listed. Trend The further studies are needed to ascertain the exact effective fraction of endogenous mediators in order to offer new idea for cardioprotective drug development.