The aim of the current study was to investigate dynamic changes in brain Nogo-A protein in rats, and the effects of mild hypothermia therapy on its expression after Cardio-Pulmonary Resuscitation (CPR). Western-blotting and neurological scoring of 45 rats subjected to cardiac arrest and CPR were performed to investigate the expression of Nogo-A protein in the hippocampus and cortex 6 h, 12 h, 24 h, 48 h, and 72 h after restoration of spontaneous circulation (ROSC). Nogo-A expression levels gradually increased from 6 h after CPR in the brain. In the hippocampus and cortex, Nogo-A exhibited a unimodal waveform-first it increased, but then it decreased. It peaked at 24 h in the hippocampus, and at 48 h in the cortex. The expression of Nogo-A in the mild hypothermia group was significantly lower at 12 h (p<0.05). Mild hypothermia can reduce the expression of Nogo-A protein in the hippocampus and cortex after CPR, which may be one of the mechanisms that play a role in cerebral protection.