Objective To investigate the effect of laminarin (Lam) on the protein expression of glucose regulated protein-78 (GRP-78) and cysteine-dependent aspartate-specific protrases 12 (Caspase12) in rat model of myocardial ischemia-reperfusion injury (MI/RI) and whether it has protective effect on rat myocardium. Methods Thirty-two male SD rats were randomly divided into 4 groups:sham operation group, MI/RI group, low- and high-dose Lam treatment groups. The rat MI/RI model was established by left coronary artery ligation. The serum content of creatine kinase isoenzyme MB (CK-MB) was measured by enzyme-linked immunosorbent assay (ELISA), the content of myeloperoxidase (MPO) in the myocardial tissue was measured by colorimetric assay, and the protein expression levels of GRP78, Caspase 12, B-cell lymphoma-2 (Bcl-2) in myocardium was detected by Western blotting. The pathomorphological changes of myocardial tissue were observed by light microscopy. Myocardial infarction area was measured by Evans Blue and 2,3,5-triphenyltetrazolium chloride (TTC) double staining. SPSS statistics 21.0 was used to perform the statistical analysis. Results The low- and high-dose Lam treatment groups had significantly decreased serum level of CK-MB [(72.71±5.63) vs (59.79±9.67) vs (93.74±5.37)U/L], myocardial content of MPO [(58.92±4.88) vs(46.06±5.74) vs(72.66±3.40)U/L] and protein levels of GRP-78 [(0.81±0.01) vs (0.66±0.01) vs (1.13±0.02)] and Caspase 12 [(0.82±0.06) vs (0.62±0.02) vs (1.45±0.10)], but obviously enhanced expression of Bcl-2 [(1.19±1.10) vs (1.41±0.02) vs (1.01±0.04)] when compared with the MI/RI group (all P<0.01). The myocardial tissue damage in the Lam treatment groups was alleviated to different extents than that in the MI/RI group. And the area of myocardial infarction was remarkably reduced in the low-and high-dose Lam treatment groups than the MI/RI group [(55.36±2.47)% vs (46.63±2.10)% vs (38.40±2.07)%, P<0.05]. Conclusion Lam can alleviate MI/RI and exerts protective effect on the injury in rats. The mechanism may be that Lam can inhibit the overexpression of GRP-78, reduce the activation of apoptosis pathway mediated by endoplasmic reticulum stress, down-regulate the apoptosis pathway of Caspase 12 and enhance the expression of Bcl-2, and thus inhibit the apoptosis of cardiomyocytes.