Rut-bpy is a novel nitrosyl-ruthenium complex releasing NO into the vascular system. We evaluated the effect of Rut-bpy (100 mg/kg) on a rat model of brain stroke. Forty rats were assigned to four groups (Saline solution [SS], Rut-bpy, SS+ischemia-reperfusion [SS+I/R] and Rut-bpy+ischemia-reperfusion [Rut-bpy+I/R]) with their mean arterial pressure (MAP) continuously monitored. The groups were submitted (SS+I/R and Rut-bpy+I/R) or not (SS and Rut-bpy) to incomplete global brain ischemia by occlusion of the common bilateral carotid arteries during 30 min followed by reperfusion for further 60 min. Thirty minutes before ischemia, rats were treated pairwise by intraperitoneal injection of saline solution or Rut-bpy. At the end of experiments, brain was removed for triphenyltetrazolium chloride staining in order to quantify the total ischemic area. In a subset of rats, hippocampus was obtained for histopathology scoring, nitrate and nitrite measurements, immunostaining and western blotting of the nuclear factor- κB (NF-κB). Rut-bpy pre-treatment decreased MAP variations during the transition from brain ischemia to reperfusion and decreased the fractional injury area. Rut-bpy pre-treatment reduced NF-κB hippocampal immunostaining and protein expression with improved histopathology scoring as compared to the untreated operated control. In conclusion, Rut-bpy improved the total brain infarction area and hippocampal neuronal viability in part by inhibiting NF-κB signaling and helped to stabilize the blood pressure during the transition from ischemia to reperfusion.