Abstract: Objective To investigate the protective effect of target temperature management (TTM) combined with prostaglandin E1 (PGE1) on ischemia/reperfusion (I/R) injury of cerebral micro-vascular endothelium cell (CMEC) in the return of spontaneous circulation (ROSC) rats with successful cardiopulmonary resuscitation. Methods Transoesophageal cardiac pacing with alternating current was used to induce ventricular fibrillation in rats. Five groups were set: Sham group (S group), ROSC group (R group), PGE1 group (P group), TTM group (T group) and PGE1/TTM group (PT group). Cell edema and micro-thrombus formation in cerebral tissue were evaluated through HE staining. I/R injury of CMEC was evaluated through CD34/TUNEL and vascular endothelial (VE)-cadherin/VE growth factor receptor double fluorescent immunohistochemistry staining. VE-cadherin mRNA and vascular cell adhesion molecule-1(VCAM-1) mRNA expression in cerebral tissue lysate was analyzed by fluorescence quantitative PCR. Results TTM, PGE1 and PGE1/TTM could significantly improve cerebral interstitial edema, micro-thrombus, and inflammatory cells infiltration in the brain tissue, and reduce the apoptosis and VE-cadherin protein loss of CMEC. PGE1/TTM showed better protective effect. These 3 interventions also inhibited the rapid elevation of VE-cadherin mRNA (0.5 h) and VCAM-1 mRNA (4 h and 8 h) expression (P1 and TTM could alleviate I/R injury of CMEC from ROSC rat after CPR separately, while PGE1/TTM combined intervention might have synergistic better effect.