Abstract: AIM:To study the effects of hyperglycemia on oxidative stress and ischemia/reperfusion (I/R) myocardial injury in rats and the possible mechanisms. METHODS: Rats were subjected to 30 min of myocardial ischemia and 6 h of reperfusion and were randomly assigned to sham group, vehicle group (saline throughout ischemia and reperfusion period) or high glucose (HG) group (administration of 500 g/L glucose by i.v. infusion during ischemia and reperfusion period). Blood glucose levels were monitored throughout the experiments. Myocardial infarct size (IS) and serum myocardial enzymogram of rats were determined after the experiments. Apoptotic index (AI), caspase 3 activity, thioredoxin-interacting protein (Txnip) protein level and thioredoxin (Trx) activity were detected in I/R rats and were determined after the experiments. Apoptotic index, caspase 3 activity, superoxide, gp91phox, malondialdehyde (MDA), superoxide dismutase (SOD), and Txnip protein level of myocardium were also detected. RESULTS: Compared with vehicle group, HG group had significantly enlarged infarct size as well as increased creatine kinase, lactate dehydrogenase levels, AI and caspase 3 activity (P<0.05). At the same time, hyperglycemia increased oxidative stress as expressed by increased superoxide, gp91phox and MDA (P<0.05). Hyperglycemia increased Txnip protein expression in ischemia/reperfusion myocardium and decreased Trx activity. However, Trx protein was not affected. CONCLUSION: Hyperglycemia induces Txnip expression and decreases Trx activity in I/R myocardium. The resultant increased oxidative stress may be one of the mechanisms responsible for the exacerbated rat I/R myocardial injury induced by hyperglycemia.