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Myocardial infarction (MI) is a frequent and severe manifestation of ischemic heart disease. We investigated the changes of protein in chronic MI which was occurred with long-term ischemia, without reperfusion. Guaruhaebaekbaekju-tang(瓜蔞薤白白酒湯, GHT) is an established traditional Chinese medicine that is widely used for the treatment of cardiac function, although its mechanisms remain unclear. GHT (100 or 200 mg/kg/day) was administered to rats immediately after coronary artery ligation for 8 weeks. After being sacrificed, the effect of GHT on cardiac fibrosis was confirmed by cardiac function and histological studies. As a result, the biomarker for detecting MI, lactate dehydrogenase (LDH), creatine kinase myocardial band (CK-MB) and Creatine Phosphokinase (CPK) enzymes, were significantly decreased by GHT. Heart function was evaluated by cardiac ultrasound to determine the effect of GHT on left ventricular dysfunction. MI group have decreased EF (Ejection fraction) as well as FS (Fractional shortening), compared to HT group. Additionally, left-ventricular (LV) dysfunction and dilatation were attenuated in the GHT group compared with MI group. In addition, protein expression levels the effect of GRT on cardiac fibrosis was confirmed by reducing the expression of transforming growth factor β (TGF-β) and collagen 1. This is thought to appear through inhibition of the TGF-β/p-Smad 2 pathway. Additionally, GHT reduced the Masson's trichrome and picrosirius red staining intensity in left ventricle of the MI group. Therefore, these findings suggest tha GHT has protective effects via inhibition of TGF-β/p-Smad 2 pathway, which is associated with improvement of myocardial fibrosis in rats with MI. These results suggest that GHT has a protective effect on heart failure by alleviating cardiac hypertrophy, myocardial fibrosis, cardiac dysfunction caused in MI model. This study was supported by a National Research Foundation of Korea (NRF) Grant funded by the Korean government (MSIP) (2017R1A5A2015805) (2021R1A2C1010859). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.