BACKGROUND To investigate the effects of early enteral nutrition (EN) supplemented with Arginine (Arg) on intestinal mucosal immunity in severely burned mice. METHODS Forty-four mice were randomly assigned into four groups: a sham injury+EN group (n=10), a sham injury+EN+Arg group (n=10), a burn+EN group (n=12), and a burn+EN+Arg group (n=12) and the mice in two experimental groups received a 20% total body surface area (TBSA), full-thickness scald burn on the back. Then, the burned mice were given a 175 kcal/kg body wt/day of conventional enteral nutrition or an isonitrogenous and isocaloric enteral nutrition supplemented with Arg by gastric gavage for 7 days. There was isonitrogenous and isocaloric intake in two experimental groups. The mice in two control groups received the same procedures as above, except for burn injury. On day 7 after injury, all mice among four groups were euthanized and the entire intestine was harvested. Intestinal immunoglobulin A (IgA) levels, total lymphocyte yield, and lymphocyte subpopulations in Peyer's patches were analyzed. Levels of IFN-gamma, IL-2, IL-4 and IL-10 in gut homogenates were also measured by ELISA. RESULTS Total lymphocyte yield, numbers of lymphocyte subpopulations, and intestinal IgA levels in the EN+ARG group were higher than those in the EN group (p<0.05). Levels of gut tissue cytokines were significantly altered with enteral Arg supplementation: levels of IL-4 and IL-10 were increased, and levels of IFN-gamma and IL-2 declined, when compared with the EN-fed mice (p<0.05). CONCLUSIONS The results of this study suggested that enteral nutrition supplemented with Arg has changed the cytokine concentrations in intestinal homogenates from a pro- to an anti-inflammatory profile, increased sIgA levels and changed lymphocytes in severely burned mice.