PURPOSE: This study investigated the effects of glycyrrhizin, a potent antioxidant, on tissue injury caused by ischemia/reperfusion (I/R) of the gut. METHODS: I/R injury of the intestine was caused by clamping both the superior mesenteric artery and the celiac trunk for 45 min followed by release of the clamp allowing reperfusion for 1 or 6 h. RESULTS: Administration of glycyrrhizin, significantly reduced the (a) fall of mean arterial blood pressure, (b) mortality rate, (c) myeloperoxidase (MPO) activity, (d) production of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta)], (e) histological evidence of gut injury, (f) immunoreactivity of nitrotyrosine, (g) poly ADP-ribose (PAR) formation, (h) the expression of ICAM-1 and P-selectin, (i) activation of nuclear factor-kappaB (NF-kappaB) and (j) signal transducer and activator transcription-3 (STAT-3) induced by splanchnic artery occlusion-reperfusion shock. CONCLUSIONS: This study demonstrates that glycyrrhizin exerts multiple protective effects in splanchnic artery occlusion-reperfusion shock.