Abstract: AIM: To detect the effects of S-nitrosoglutathione (GSNO) on myocardial ischemia reperfusion injury in diabetic and non-diabetic mice. METHODS: One hundred and twenty male mice were divided into six groups: control+sham, DM+sham, control+MI/R+vehicle, DM+MI/R+vehicle, control+MI/R+GSNO, and DM+MI/R+GSNO. Mice were anesthetized with 2% isoflurane and myocardial ischemia was produced by temporarily exteriorizing the heart via a left thoracic incision and placing a 6-0 silk suture slipknot around the left anterior descending coronary artery. Ten minutes before reperfusion, mice were randomized to receive vehicle or GSNO. After 30 min of ischemia, the slipknot was released and the myocardium was reperfused for 3 h (for NOx contents, nitrotyrosine content and caspase-3 activity by ELISA, O-2 contents by frozen section and apoptosis by TUNEL) or 24 h (for infarct size by TTC). RESULTS: Compared with those in group of control+sham, the contents of O-2 increased in group of DM+sham (P<0.05). Compared with those in group of control+MI/R+vehicle, the infarct size (P<0.05), myocardial apoptosis (P<0.05), caspase-3 activity (P<0.05) and the contents of nitrotyrosine (P<0.05) reduced, and the contents of NOx increased (P<0.01) in control group+MI/R+GSNO. Compared with those in group of DM+MI/R+vehicle, infarct size (P<0.01), myocardial apoptosis (P<0.05), caspase-3 activity (P<0.01), contents of nitrotyrosine (P<0.05) and NOx (P<0.05) increased in group of DM+MI/R+GSNO. CONCLUSION: GSNO reduces MI/R injury in non-diabetic mice but increases MI/R injury in diabetic mice.