In severe burns, increased intestinal permeability facilitates bacterial translocation, resulting in systemic endotoxemia and multi- organ failure. We investigated the role of burn-induced gastrointestinal dysmotility (BIGD) in promoting bacterial translocation following burn injury, and the protective effect of ghrelin in this process. We assessed gastric emptying (GE%) and intestinal transit (IT by geometric center "GC") in a 60% total body surface area scald burn rat model and measured bacterial counts in mesenteric lymph nodes (MLN) and distal small intestine by colony-forming unit per gram of tissue (CFU/g). A group of animals was treated with ghrelin or saline after burn. Scald burn was associated with a significant delay in GE (62%±4% vs 74%±4%; P=.02) and a trend of delay in intestinal transit (GC: 5.5±0.1 vs 5.8±0.2; P=.09). Concurrently, there was a marginal increase in small intestinal bacterial overgrowth (6×105 vs 2×105 CFU/g; P=.05) and significant translocation to MLN (2×102 vs 4×101 ; P=.03). We observed a negative correlation between GE and intestinal bacterial overgrowth (rs =-0.61; P=.002) and between IT and translocation (rs =-0.63; P=.004). Ghrelin administration significantly accelerated GE following burn injury (91%±3% vs 62%±4; P=.03), reduced small intestinal bacterial overgrowth, and completely inhibited translocation to MLN (0.0 vs 5×102 ; P=.01). Burn-induced gastrointestinal dysmotility is correlated with the systemic translocation of gram-negative gut bacteria that are implicated in multiple organ failure in burn patients. Therapeutic interventions to restore BIGD are warranted (Neurogastroenterol Motil, 2012, 24, 78).