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Apelin is the endogenous peptide APJ receptor,while APJ is a member of the G protein-coupled receptors family.Recent evidence strongly suggests that Apelin/APJ system influences apoptosis in various diseases through different signal pathways.In this review,we discuss the possible mechanisms by which the Apelin/APJ system inhibits apoptosis,including the phosphatidylinositol-3-kinase (PI3K)/Akt,ERK1/2,caspase signaling,and autophagy pathway.We also summarize the role of Apelin/APJ system in apoptosis in myocardial ischemia-reperfusion (I/R) injury,pulmonary artery hypertension,retinal neovascular disease,acute renal injury,skeletal homeostasis,and gastrointestinal diseases.Apelin/APJ system decreases myocardial infarction size and alleviates myocardial I/R injury by inhibiting cardiomyocytes apoptosis.However,Apelin/APJ system improves pulmonary artery hypertension via increasing apoptosis.Apelin/APJ system exerts neuroprotective effect by blocking apoptosis and participates in the recovery of retinal neovascular disease by suppressing apoptosis.Apelin/APJ system also shows anti-apoptotic effect against acute renal injury and plays a role in regulating skeletal homeostasis.In gastrointestinal disease,Apelin/APJ system plays a potential physiological role in gastrointestinal cytoprotection by regulating apoptosis.We hope that a better understanding of the Apelin/APJ system will help to discover new disease pathogenesis and find possible therapeutic targets of the Apelin/APJ system essential for various diseases.