Objective:To study the changes of inducible nitric oxide synthase expression induced by high glucose treatment and the relationship between p38 mitogen activated protein kinase and the level of iNOS expression in human retinal pigment epithelium cells. Methods:The cells were divided into control group, high glucose group, high glucose plus SB203580 group and mannitol group. Cell viability was assessed by the MTT assay. The changes of iNOS and p-p38 MAPK expressed by RPE cells were studied with immunofluorescence staining method in a qualitative way. Results:(1) The treatment of RPE cells with 33 mmol/L glucose caused an obviously decrease of cellular viability. After pretreated with SB203580, cell viability was elevated compare with high glucose group. (2)iNOS expression and the phosphorylation level of p38 MAPK were enhanced obviously by high concentration glucose. After pretreated by SB203580, the high glucose-evoked iNOS expression was significantly inhibited. Conclusion:High glucose could inhibits RPE cells proliferation. RPE cells cultured with high glucose could enhance expression of iNOS of the cells in vitro, at least in part, by activation of p38 MAPK pathway. It suggested that RPE cells under the effecting of high glucose might participate in the pathological reaction of diabetic retinopathy.