Aim To investigate the expression of P66Shc mRNA on peripheral blood monocytes （PBMs） in patients with acute myocardial infarction （AMI） and its relationship with oxidative stress. Methods According to clinical manifestations and results of coronary angiography, 67 patients were recruited to this study . They were divided into three groups: normal control group （n＝23）, stable angina pectoris （SAP）group （n＝23） and AMI group （n＝21）. The levels of serum superoxide dismutase （SOD） and malondialdehyde （MDA） activity were examined to analyze the state of oxidative stress state in all subjects. PBMs were isolated and the expression of P66Shc mRNA was determined by quantitative Real-time PCR. Results The levels of MDA and P66Shc mRNA were greatly increased and SOD were significantly decreased in AMI group in comparison with SAP and normal control group. There were no significant differences between SAP group and normal control group on the levels of serum SOD, MDA and P66Shc mRNA （P>0.05）. The expression of P66Shc was in positive correlation with the level of MDA（r＝0.49,P＝0.024）, but not with the level of SOD in AMI group. Conclusion P66Shc mRNA levels were increased in AMI patients, which may be involved in the mechanism of transition from a stable to an unstable lesion.