Recent study has showed that Ginsenoside Rg1, the mian active compound of Panax ginseng, could ameliorate oxidative stress and myocardial apoptosis in diabetes mellitus. However, the roles and mechanisms of Rgl in proliferative diabetic retinopathy (PDR) are still unclear. In the present study, we aimed to investigate the effects of Rgl on mesenchymal activation of high-glucose (HG) cultured muller cells. High glucose conditions up-regulate MMP-2, MMP-9 and down-regulate TIMP-2, and promote mesenchymal activation in Muller cells. And Rgl inhibits the HG-induced mesenchymal activation and HG-increased MMP-2 and MMP-9 and HG-decreased TIMP-2 in Muller cells. HG up-regulates Zeb1 and IncRNA RP11-982M15.8, and down-regulates miR-2113, and Rgl inhibits these effects of HG. Both inhibition of miR-2113 and over-expression of RP11-982M15.8 significantly restored the HG induced mesenchymal activasion. Taken together, our findings suggested that Rgl inhibited HG-induced mesenchymal activation and fibrosis via regulating miR-2113/RP11-982M15.8/Zebl pathway. (C) 2018 Published by Elsevier Inc.