Objective To explore the possible mechanism of Xinkang Granule in treating chronic heart failure（ CHF）. Methods Ninety Sprague Dawley（ SD） rats were randomized into a normal group（ n = 10）

a model group（ n = 16）

a control group（ n = 16）

and Xinkang low

medium and high dose groups（ n = 16 in each）. Rats in all groups were made CHF models by adriamycin vial 1. 5 mg/kg intraperitoneal injection except those in the normal group. The Xinkang low

medium and high dose groups were given 0. 5

1 and 2 g/（ kg·d） of Xinkang Granule

respectively. The control group was given 0. 06 g/（ kg·d） of Qili Qiangxin Capsule（ 芪苈强心胶囊）. The normal group and the model group were given equivalent normal saline by gavage. All groups were treated once every day for 8 weeks. Heart function of rats was examined. Cardiomyocyte apoptosis was examined by Td T-mediated d UTP nick end labeling（ TUNEL） stain. Myocardial fibrosis was examined by Masson stain. The expression levels of myocardium caspase 12（ Caspase-12）

glucose regulated protein 78（ GRP78）

CCAAT/enhancer-binding protein homologous protein（ CHOP） and mRNA were detected by methods of real-time polymerase chain reaction（ PCR） and immunohistochemistry. Results Compared with those in the model group

cardiomyocyte apoptosis and fibrosis in the Xinkang low

medium and high dose groups decreased. Compared with those in the model group

left ventricular diastolic diameter（ LVIDd）

left ventricular end systolic diameter（ LVESD）

Caspase-12

GRP78 and CHOP protein decreased in the control group

as well as the Xinkang low and medium dose groups

Caspase-12

GRP78 and CHOP mRNA decreased in the Xinkang medium dose group

but left ventricule ejection fraction（ LVEF）

fractional shortening of the left ventricular minor semi axis（ LVFS） and cardiac output（ CO） increased in the Xinkang medium dose group（ P < 0. 05）. Compared with those in the control group

LVIDd and LVESD decreased but LVEF and CO increased in the Xinkang low dose group

LVESD and Caspase-12 expression decreased but LVIDd and CHOP mRNA expression increased in the Xinkang medium dose group

and the expressions of CHOP and Caspase-12 mRNA decreased in the Xinkang low and medium dose groups（ P < 0. 05）. Conclusion Xinkang Granule might down-regulate the expressions of myocardium Caspase-12

GRP78 and CHOP

reduce endoplasmic reticulum stress apoptosis and inhibit ventricular remodeling

which might be one of the mechanisms of it in treating CHF. Low and medium dose of Xinkang Granule is more effective.