Heart failure is a serious cardiovascular disease, and the exploration of its treatment is still developing. This study explored the compatibility significance of licorice in Sini Decoction, especially its effect on drug efficacy, by establishing a rat model of heart failure. Through metabolomic analysis of rat serum samples, the regulation differences of endogenous metabolites in heart failure rats between Gancao containing and Gancao deficient Sini Decoction were compared. . The study found that licorice could significantly improve the efficacy of Sini Decoction by enhancing the regulation of key pathways such as renin-angiotensin system. These findings were further validated by Western blot experiments. These results showed that Glycyrrhiza uralensis played not only a role of reconciliation, but also a significant synergistic effect in Sini Decoction