Although angiotensin II (Ang II) plays a key role in development of organ ischemia-reperfusion injury, it remains unclear whether it is involved in development of intestinal injury following trauma-hemorrhage (T-H). Studies have shown that 17-estradiol (E2) administration following T-H improves small intestinal blood flow; however, it is unclear whether Ang II plays a role in this E2-mediated salutary effect. Male Sprague-Dawley rats underwent laparotomy and hemorrhagic shock (removal of 60% total blood volume, fluid resuscitation after 90 min). At onset of resuscitation, rats were treated with vehicle, E2, or E2 and estrogen receptor antagonist ICI 182,780 (ICI). A separate group of rats was treated with Ang II subtype-I receptor (AT1R) antagonist Losartan. At 24 hr after T-H, plasma Ang II, interleukin (IL)-6 and tumor necrosis factor (TNF)- levels, small intestine Ang II, IL-6, TNF-, intercellular adhesion molecule (ICAM)-1, cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-3 levels, myeloperoxidase (MPO) activity and AT1R expression were determined. T-H significantly increased plasma and intestinal Ang II, IL-6, and TNF- levels, intestinal ICAM-1, CINC-1 and CINC-3 levels, MPO activity and AT1R protein compared to shams. E2 treatment following T-H attenuated increased intestinal MPO activity, Ang II level, and AT1R protein expression. ICI administration abolished the salutary effects of E2. In contrast, Losartan administration attenuated increased MPO activity without affecting Ang II and AT1R levels. Thus, Ang II plays a role in producing small intestine inflammation following T-H and the salutary effects of E2 on intestinal inflammation are mediated in part by Ang II and AT1R downregulation.