Abstract: Objective To study the protective effect of Salubrinal on tunicamyiocin（TM）-induced apoptosis of primary cardiac muscle cells in suckling mice and its mechanism. Methods Primary cardiac muscle cells were isolated from mice using the modified 2-step collagenase digestion method.After pretreated with Salubrinal at different concentrations（10μmol,20μmol and 40μmol） for 30min followed by addition of 5μg/ml tunicamyocin（TM）,cardiac muscle cells were incubated for 24h.Apoptosis of the cells was detected by flow cytommetry and TUNEL,respectively.Changes in expression of Caspase-12 during apoptosis were detected by Western blot. Results The apoptosis rate and apoptosis index of cardiac muscle cells and the expression of Caspase-12 in cardiac muscle cells were significantly lower after pretreatment with Salubrinal than after treatment with TM alone. Conclusion Salubrinal protects cardiac muscle cells against TM-induced apoptosis by inhibiting the stress-associated apoptosis pathway in the endoplasmic reticulum.