The aim of the present investigation was to evaluate the effect of an extract from Corydalis yanhusuo W.T., a Chinese herbal medicine, on ischemia/reperfusion (I/R) injury and to determine the mechanism(s) involved. In rats, the left anterior descending (LAD) coronary artery was occluded for 30 min and then reperfused for 6 h. 0.5% carboxymethyl cellulose sodium was used as a vehicle (I/R control group) and Corydalis yanhusuo rhizoma extract (I/R + CY 200, 100 mg/kg groups) were given. Infarct size and hemodynamic parameters were measured. Apoptosis was detected quantitatively by the terminal transferase dUTP nick end-labeling (TUNEL) method and confirmed by DNA laddering on agarose gel. The expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax proteins was visualized by western blot analysis. In contrast to the I/R control group, administration with CY 200 mg/kg resulted in a significant reduction in the infarct size and an improvement in heart function as evidenced by higher LVSP and +/-dp/dtmax. TUNEL-positive cells in the ischemic myocardium were also significantly reduced in the I/R + CY 200, 100 mg/kg groups, consistent with little DNA laddering in these two groups. Furthermore, greater Bcl-2 and attenuated Bax expression was found in the CY treated rats. These results suggest that the protective effect of Corydalis yanhusuo on myocardial I/R injury is closely associated with the inhibition of myocardial apoptosis through modulation of the Bcl-2 family.