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AIM:To study p42/p44 mitogen-activated protein kinases(MAPK)signal transduction pathway effect on vascular endothelial growth factor(VEGF)expression induced by elevated glucose concentration in cultured human retinal pigment epithelium(hRPE). <p>METHODS:hRPE cells were cultured and divided into four groups: normal glucose group(NG)(5.6mmol/L), high glucose group(HG1:15mmol/L D-glucose,HG2:20mmol/L D-glucose,HG3:30mmol/L D-glucose), PD98059 group: hRPE cells were treated by an efficient and selective inhibitor PD98059(20μmol/L)of p42/p44MAPK signal transduction pathway and solvent dimethyl sulfoxide group(DMSO group). The expression of VEGF and pigment epithelium derived factor(PEDF)mRNA was detected by RT-PCR. VEGF protein expression in cultured hRPE supernatants was detected by enzyme-linked immumosorbent assay(ELISA). <p>RUSULTS:VEGF mRNA and protein expression induced by elevated glucose concentration increased significantly. VEGF mRNA and protein expression were restrained in PD98059 group. Ratio of(VEGF/β-actine)/(PEDF/β-actine)in PD98059 group decreased significantly compare with that in high glucose group. <p>CONCLUSION:p42/p44MAPK signal transduction pathway might play a part in VEGF expression induced by elevated glucose concentration in cultured hRPE cells.