Aim The incidence of stroke in diabetes is increasing seriously,which is associated with endothelial dysfunction and increased inflammation in carotid artery.Our study is to investigate the effect of c-Jun amino-terminal kinase(JNK) specific inhibitor SP600125 on carotid endothelial function and monocyte chemotactic protein-1(MCP-1) expression in type 1 diabetes. Methods Animals were divided into five groups in this study.The 1st group was C57BL/6 wild type male mice;the 2nd group was INS2AKITA male mice,intraperitoneal injection with 0.9% normal saline(NS) each day for 8 weeks;the 3rd,4th,5th group were INS2AKITA male mice,intraperitoneal injection with SP600125 10 mg/kg,20 mg/kg,30 mg/kg respectively each day for consecutive 8 weeks.Then the mice were killed and sreum myeloperoxidase(MPO),malondialdehyde(MDA),nitric oxide(NO),total nitric oxide synthase(TNOS) were measured.HE staining was performed in carotid artery and immunohistochemistry was performed to investigate MCP-1 protein expression in endothelial cells of carotid artery.P-JNK,JNK,MCP-1 protein expression in carotid artery was measured by Western blot,signal transducer and activator of transcription-1(STAT-1) DNA binding activity was assayed by electrophoretic mobility shift assay(EMSA). Results Compared with wild type mice,serum MPO and MDA expression increased prominently(P<0.05),whereas TNOS,NO decreased and p-JNK/JNK,MCP-1 expression increased significantly in INS2AKITA mice(P<0.05);STAT-1 DNA binding activity increased prominently in type 1 diabetic group compared with that in control group(P<0.05).Compared with type 1 diabetic mice,after treatment with SP600125,MPO decreased and NO,TNOS increased and p-JNK/JNK,endothelial MCP-1 expression decreased(P<0.05).The effects of SP600125 on MPO,NO,TNOS,MCP-1 were increased accordingly as the dose of SP600125 increased.As the dose of SP600125 increased,MCP-1 protein expression decreased 21.82%,39.09%,68.18% respectively;STAT-1 DNA binding activity decreased 25.70%,33.20%,61.29% respectively compared with type 1 diabetic mice. Conclusions JNK specific inhibitor SP600125 could inhibit STAT-1 DNA binding activity,thus increase serum NO and TNOS,and improve carotid diastolic function.SP600125 could also decrease MCP1 and MPO in a dose-dependent manner.The results also showed JNK signal pathway is associated with carotid endothelial dysfunction and inflammatory expression via activation of STAT-1 in type 1 diabetes.Our study provides a novel pharmacologic agent to prevent the promotion of macrovascular complication in type 1 diabetes.