Myocardial remodeling is one of the main mechanism which leads to chronic heart failure (CHF). Thus, the drugs which suppressed the process of myocardial remodeling showed better clinical outcomes to deal with CHF. Total glucosides of paeony (TGP) which is used in many traditional Chinese medicines (TCM) exhibited promising ethno-pharmacological effects such as immunosuppressant, anti-inflammatory, analgesia, anti-stress, liver disease, allergies, anticoagulant, and cardiovascular activities. This study aims to investigate the effects of TGP on myocardial remodeling by regulating the nuclear factor kappa B cells (NF-κB) pathway. SD rats were selected and divided into five groups (n = 8), control, sham-operated, Captopril, low dose TGP and high dose TGP respectively. The pressure-overload method was adopted by abdominal aorta ligation to induce the CHF. Furthermore, collagen fibers detected by picrosirius red staining and expression of NF-kB, TGF-β1 by immunohistochemistry and observed under a polarized microscope and assessed by image-pro plus 6.0. Matrix metalloproteinase’s (MMP)-2, -9 mRNA levels by reverse transcription PCR (RT-PCR), the concentration of angiotensin II was determined by radioimmunoassay and ELISA was employed to determine the cytokine IL-1β. It was observed that TGP could relieve myocardial remodeling in rats induced by abdominal aorta ligation and decrease the level of angiotensin II and I/III collagen ratio, pathogenic cytokines and inhibit the expression and activities of MMPs. Consequently, the observations suggested that myocardial remodeling was mediated by the NF-κB pathway.