Abstract: Objective To study the effect of Bacillus subtilis lysis converting enzyme 9 (PCSK9) on myocardial endoplasmic reticulum stress and its possible mechanism, and to provide a new research direction for clinical research. Methods Thirty healthy male SD rats were selected to establish myocardial ischemia-reperfusion model. According to the method of random number table, rats were divided into three groups:sham operation group, model group and PCSK9 group. Twenty-four hours after the successful modeling, the PCSK9 group rats were injected subcutaneously with 30 μg PCSK9, while the sham operated group rats and the model group rats were injected subcutaneously with normal saline of equal volume. LVEDP, myocardial infarct area rate, LDH, CK-MB, CK, apoptosis rate, proliferation, GRP78, CHOP, and cleaved caspase 3 levels were examined at the end of the intervention. Results The LVEDP[(8.83±0.28) mm Hg] and myocardial infarction area rate[(15.21±4.75)%] in the PCSK9 group were lower than those in the model group[(13.65±0.38) mm Hg, (37.35±8.16)%] and higher than those in the sham operation group[(7.72±0.43) mm Hg, 0%], F=731.290, t=7.420, all P<0.001. In the PCSK9 group, LVSP[(127.94±7.67) mm Hg] was higher than that in the model group[(79.84±6.44) mm Hg], lower than that in the sham operation group. The prognosis of the sham operation group was (145.53±9.08) mm Hg (F=189.830, P<0.001). The apoptosis rate, LDH, CK-MB, CK level, GRP78, CHOP and cleaved caspase-3 protein expression in the model group and the PCSK9 group were higher than those in the sham operation group, and the cell proliferation rate was lower than that in the sham operation group (all P<0.05). Conclusion PCSK9 can regulate GRP78, CHOP and caspase-3 protein, inhibit the stress of myocardial endoplasmic reticulum and improve the cardiac function and myocardial infarction.