BACKGROUND: Norepinephrine administration is controversial during hemorrhagic shock resuscitation to stabilize mean arterial pressure (MAP) level because it could have deleterious effects on local circulations. The authors investigated the effect of norepinephrine on intestinal microcirculation during fluid resuscitation in uncontrolled hemorrhagic shock. METHODS: Mice (n = 6 per group) submitted to an uncontrolled hemorrhagic shock by tail section were randomly assigned to a resuscitation with fluid but without norepinephrine to target a MAP level of 50 mmHg (FR50) or 60 mmHg (FR60) or a resuscitation with fluid and norepinephrine to target a MAP level of 50 mmHg (FRNE50) or 60 mmHg (FRNE60). Intestinal microcirculation was observed by intravital microscopy. RESULTS: Fluid requirements were lower in groups resuscitated with fluid and norepinephrine than in groups resuscitated with fluid without norepinephrine (74.6???45.1 in FR50 vs. 28.1???10.0 ?l/g in FRNE50; P = 0.004 and 161.9???90.4 in FR60 vs. 44.5???24.0 ?l/g in FRNE60; P = 0.041). Blood loss was not statistically different between FR50 and FRNE50 (14.8???8.3 vs. 8.5???2.9 ?l/g; P = 0.180) but was significantly lower in FRNE60 than in FR60 (10.1???4.2 vs. 22.6???9.6 ?l/g; P = 0.015). This beneficial effect was associated with the restoration of intestinal microcirculation to the same extent in fluid resuscitated groups without norepinephrine (FR50 and FR60) and fluid resuscitated groups with norepinephrine (FRNE50 and FRNE60). CONCLUSIONS: During MAP-directed resuscitation of uncontrolled hemorrhagic shock, the administration of norepinephrine decreased blood loss and fluid requirements while preserving intestinal villi microcirculation.