〔Abstract〕 Objective To investigate the effect and mechanism of celecoxib on retinal vascular endothelial growth factor(VEGF) in rats with diabetic retinopathy. Methods Forty-five SD rats were divided into normal control group(NC),diabetic retinopathy group(DR), celecoxib intervention diabetic retinopathy group(DR+C). The diabetic model was established by intraperitoneal injection of 1% STZ. After one month, celecoxib(50 mg/kg) was given intragastric administration(1/day) in the DR+C group.Two months later, serum total cholesterol(TC) and insulin were detected.The histopathological changes of the retina were observed.The expression of junctional adhesion molecule-like protein(JAML),VEGF and their signal pathway proteins and the distributions of interleukin-10(IL-10), vascular cell adhesion molecules-1(VCAM-1) were detected by Western blot. HUVEC cells were divided into normal glucose group(NG),high glucose group(HG) and high glucose plus celecoxib group(HG+C) to detect the expression of the above proteins. Results Compared with DR,retina in DR+C group was thinner. The retina in the DR+C group was thicker than that in the NC group. The levels of retinal JAML,phosphatidylinositol kinase3(PI3K),phosphorylphosphatidylinositol kinase3(P-PI3K), hypoxia-inducible factor1-α(HIF1-α),and VEGF in DR+C group were lower than those in DR group, while higher than those in NC group.The expression of retinal IL-10 and VCAM-1 decreased.The content of TC in DR+C and DR group was higher than those in NC group(P<0.01), while the content of insulin in DR+C and DR group was lower than thlse in NC group(P<0.001). Compared with HG group, the expressions of JAML,PI3K,P-PI3K,HIF1-α,VEGF in HG+C group decreased, but was higher than those in NG group.There was no significant difference in PI3K among the three groups. Conclusion Celecoxib can decrease the expression of VEGF,IL-10, VCAM-1 in retina of DR rats, which may be related to the PI3K/HIF1-α signaling pathway mediated by JAML.