Hyaluronic acid, an important component of extracellular matrix, is up-regulated in intestinal injury to promote wound healing. Here we investigated the roles of hyaluronic acid on different enteritis or intestinal infection models and found that oral administration of hyaluronic acid improved the ability of mice to control the infection of pathogen, including Listeria monocytogenes, Citrobacter rodentium and Enteropathogenic Escherichia coli. These results indicate that hyaluronic acid protects host from gastric infection.