In the present study, we, therefore, investigate the hypothesis that RA plays a neuroprotective role through the abrogation of HMGB1 release and NF-κB activation triggered by tumor necrosis factor-α (TNF-α) and ameliorates diabetic rats with MCAO-induced cerebral ischemia/reperfusion injury. The gene discussed is HMGB1; the disease is brain ischemia.