Shenfu decoction (SFD) is a well-known important traditional Chinese medicine prescription that has been used to treat chronic heart failure (CHF) for many years in China. However, its holistic therapeutic effects and mechanism are not yet well understood. Here, a UPLC/TOF-MS-based metabonomic study was conducted to explore potential biomarkers to increase the understanding of CHF and to assess the integral efficacy of SFD for CHF in rats. Principal component analysis was used to investigate the global metabonomic alterations and to evaluate the therapeutic effects of SFD in rats. Clear separations were observed not only in the comparison of dynamic trajectories but also in the comparison of the metabolite profiles of the normal controls, the model group (CHF), the sham surgery group and the SFD-treated group. The results indicated that SFD exerted therapeutic efficacies for CHF, which were in accordance with the results of the echocardiographic and haemodynamic assay. Furthermore, 16 potential biomarkers from urine samples and 13 potential biomarkers from serum samples of CHF rats were identified and were mainly related to inflammation and to dysfunction of amino acids and energy metabolism. The therapeutic effects of SFD on CHF were partially due to the restoration of these disturbed pathways. This study provides a useful approach for exploring the mechanism of myocardial infarction (MI)-induced CHF and for evaluating the efficacy of SFD on CHF. (C) 2014 Elsevier B.V. All rights reserved.