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To investigate whether hydrogen sulfide (H2S) protect the heart against myocardial ischemia/reperfusion (I/R) injury by inhibiting apoptosis caused by I/R-induced excessive endoplasmic reticulum stress (ERS), I/R rat model was reproduced by ischemia 30 minutes followed by reperfusion2 hours.H2S preconditioning (SPC) by injected (i.p.) sodium hydrosulfide (NaHS) before 10min of myocardial ischemia, and H2S postconditioning(S-postC) by injected (i.p.) NaHS after 30 min of myocardial ischemia and within reperfusion 10min.At the end of the reperfusion, myocardial infarct size, myocardial apoptosis were determined.ERS related proteins GRP78 and CHOP levels were assayed by western blotting.We found that Both SPC and S-postC significantly reduced myocardial infarct size and apoptotic rate caused by I/R.Meanwhile, both SPC and S-postC decreased GRP78 and CHOP protein level induced by I/R.This finding suggested that cardioprotection of H2S may involve inhibiting apoptosis caused by I/R induced excessive ERS.