To observe the effect of Shen Yuan Dan(SYD) on Grp78 and CHOP expression in ischemia-reperfusion myocardium cells. Methods: To culture cardiomyocytes from newborn rats, and then divided them into normal group, model group, SYD group and blank serum group. Ischemia (2 h) / reperfusion (4 h) model was established by tri-gas incubator. Real-time polymerase chain reaction (PCR) were used to detect the Grp78 and CHOP gene expression levels. Results: The Grp78, CHOP expression levels in model group were significantly increased (P<0.01). Compared with model group, Grp78 and CHOP were significantly decreased in 10% SYD group (P<0.05). Levels of Grp78 and CHOP has no obvious change between 10% blank serum group and model group. Conclusion: SYD can reduce endoplasmic reticulum stress in myocardial cell apoptosis and protect myocardial cells.