Ginseng panaxadiol (PD) derivatives have been reported to retain anti-diabetic effect. Diabetic retinopathy is one of major complications of diabetes mellitus, which is induced by cell apoptosis of retina. Thus, this study was conducted to examine the protective effect of ginsenoside Rb2, a major component of PD derivatives, in the high glucose-induced cell loss of ARPE cells (a human retina pigment epithelial cell-line). In present study, high glucose induced the decrease of cell viability, which was blocked by the treatment of ginsenoside Rb2 (＞10-6 g/㎖). In addition, high glucose increased the expression of Bax and decreased the expression of Bcl-2 expression, which was prevented by the treatment of ginsenoside Rb2. Furthermore, high glucose increased lipid peroxide formation and cyclooxygenase-2 (COX-2) expression, which was also blocked by the treatment of ginsenoside Rb2. In conclusion, ginsenoside Rb2 prevented high glucose-induced apoptosis via the decrease of lipid peroxide (LPO) and COX-2 expression in ARPE cells.