Objective To investigate Kir4.1 expressions in Muuml;ller cells under high glucose conditions and treatment of pigment epitheliumderived factor (PEDF）. Methods Cultured rat Muuml;ller cells were divided into control group (5 mmol/L glucose), high glucose group (25 mmol/L glucose), PEDF treatment group (25 mmol/L glucose+100 ng/ml PEDF) and intervention control group（25 mmol/L glucose+phosphate buffer solution）. Kir4.1 expressions were measured by Western blot and real-time reverse transcription polymerase chain reaction (RT-PCR). Reactive oxygen species (ROS) productions were measured using 2prime;7prime;dichlorofluorescin diacetate and glutathione peroxidase （GPx）expressions were studied by real-time RT-PCR. Results By Western blot and real-time RT-PCR, it was found the expressions of Kir4.1 decreased obviously under high glucose conditions (real-time RT-PCR: t=4.12, P＜0.05; Western blot: t=3.53,P＜0.05); simultaneously, ROS generation was increased （t=3.76,P＜0.05）and GPx level was decreased （t=3.18,P＜0.05）. PEDF treatment inhibited the high glucose-induced Kir4.1 down regulation (real-time RT-PCR: t=3.66, P＜0.05; Western blot: t=6.43,P＜0.01) and decreased ROS generations （t=4.11,P＜0.05） and increased GPx levels (t=5.12,P＜0.01）. Conclusions The high glucose can supress Kir4.1 expressions in Muuml;ller cells by oxidative stress, and PEDF can ameliorate these effects.