To the best of our knowledge, the present study is the first to report the inhibitory effect of the ghrelin/GHSR axis on the E2F1/NF-κB signaling pathway in a rat model of sepsis, which implies that the protective effect of ghrelin/GHSR axis on sepsis-induced intestinal barrier dysfunction was mediated by eliminating the activity of E2F1/NF-κB signaling pathway. This evidence concerns the gene GHSR and Sepsis.