Objective To investigate the underlying mechanism through which heme oxygenase-1 (HO-1) protects intestine against inflammation in rats with heart failure. Methods Heart failure model was established in male Wistar rats by myocardial infarction (MI) with coronary ligation. These model rats were randomized into 3 experimental groups (10 rats in each group): Myocardial infarction (MI), MI＋cobalt protoporphyrin(Copp), and MI＋stannum＋mesoporphyrin Ⅸ dichloride (SnMP; a HO-1 inhibitor) groups, receiving intra-peritoneal injection of saline, cobalt protoporphyrin solution, and stannum mesoporphyrin Ⅸ dichloride solution, respectively. Another 10 rats served as normal controls and received intraperitoneal injection of normal saline. After 8 weeks, the endotoxin level in portal vein and inferior vena cava, the expression of HO-1, and the contents of carbon monoxide (CO), tumor necrosis factor (TNF)-α, and interleukin-10 in the intestine were determined by Western blotting, colorimetry, and enzyme-linked immunosorbent assay (ELISA). Results Compared with MI group, MI+Copp group had significantly elevated HO-1 and CO expression, reduced endotoxin, milder inflammation in the intestine, and these benefits were abolished by SnMP, with obviously decreased CO, elevated endotoxin and severer intestinal inflammation. Conclusion HO-1 suppresses intestinal inflammation, which may be associated with CO.