Abstract： Objective To clarify the role ofzonula occludens-1 (ZO-1) in early brain injury (EBI) after subarachnoid hemorrhage (SAH) and regulatory mechanism of c-Jun N-terminal kinase (JNK)to discuss the molecular mechanism of SAH-induced blood-brain barrier (BBB) dysfunction. Methods Seventy-two male SD rats were randomly assigned to sham-controlled, SAH, SAH+SP600125 (the inhibitor of JNK) and SAH+ dimethyl sulfoxide (DMSO) groups. SAH models were induced by injection of autologous blood into the cisterna magna of rats, and they were subsequently sacrificed 24 h later. The brain water content was measured, and BBB disruption was evaluated by Evans blue dye;immunohistochemistry was employed to compare the expressions of ZO-1 and JNK. Results As compared with the sham-controlled group, the SAH group 24 h after the success of model making was detected a significant increase of water content, obviously increased Evans blue dye extravasation,especially in the brain stem and cerebellum (P＜0.05) and both structural damage and neuronal damage were noted; the mean optical density of immunohistochemistry showed a strong increase of JNK expression while a obvious decrease of ZO-1 expression was noted in the SAH group 24 h afar the success of model making (P＜0.05). Treatment with SP600125 could significantly reduce the water content, decrease the Evans blue dye extravasation, inhibit the JNK expression and increase the ZO-1expression as compared with those in the SAH and SAH+DMSO groups (P＜0.05), while no significant difference was noted as compared with those in the sham-controlled group (P＞0.05). Conclusion SAH activates the phosphorylation of JNK, and represses the transcription and translation of ZO-1,subsequently, opens the tight junction and causes brain edema by redistribution of transmembrane proteins and rearrangement ofcytoskeletal proteins, therefore, EBI appears. However, treatment with SP600125 can reverse the above-mentioned processes and improve the outcome of EBI.