OBJECTIVE To investigate the effect of Guanxinning tablets(GXN) on early heart failure model rats, and to explore the protective mechanism of GXN on heart failure rats from the perspective of intestinal flora. METHODS Six rats who underwent sham operation were set as sham operation group. Took 80 SD rats to undergo aortic arch stenosis and established a heart failure rat model. The surviving rats were divided into 4 groups, namely the model control group, the positive control group(captopril tablets 12.5 mg·kg–1), high-dose and low-dose of GXN group(600, 1 200 mg·kg–1). The 4 groups were administered continuously for 8 weeks. Cardiac ultrasonography was performed every 4 week. Serum NT-proBNP, hs-CRP, IL-6, TNF-α, SOD and MDA levels were measured. The effects of GXN on the structure and function of intestinal flora were observed based on the high-throughput sequencing technology and bioinformatics analysis of 16S gut microbiome. RESULTS Compared to the model control group, after giving different doses of GXN, the survival rate of rats increased, and the thickness of the ventricular wall decreased to varying degrees. The weight of the heart and coefficient of the heart were all reduced. GXN could also reduce the level of inflammatory factors, inhibit the level increase of NT-proBNP in rats, and increase the activity of serum SOD. In addition, GXN intervention could significantly improve the intestinal flora diversity of rats with heart failure, the possible target genera of GXN were Akkermansia genera, Phascolarctobacterium genera and Oxalobacter genera. The effect of GXN on intestinal function in rats with heart failure might be concentrated in non-homologous end-joining, influenza A, carotenoid synthesis, indole alkaloids biosynthesis, betalain biosynthesis, renin-angiotensin system and other biological pathways. CONCLUSION The protective effect of GXN on early heart failure rats may be related to the regulation of intestinal flora pathway.