AIM: To investigate the mechanism of proliferation effect induced by (R,R)-XY-10 and (S,S)-XY-10 on retinal pigmented epithelial cells (ARPE-19). · METHODS: Human retinal pigmented epithelial cells (ARPE-19) and human umbilical vein endothelial cells (HUVECs) were used to investigate the effect of (R,R)-XY-10 and (S,S)-XY-10 on cell growth, and their mechanisms of proliferative action by using ERK, AKT, PI3K, Protein kinase C (PKC) and Nitric oxide synthase (NOS) inhibitors. · RESULTS: (R,R)-XY-10 and (S,S)-XY-10 dose-dependently increased ARPE-19 cell proliferation, but not on HUVECs. When treated with proliferative inhibitors, H-7 (5μmol/L), hypericin (20μmol/L), PD98059 (2μmol/L), LY294002 (50μmol/L), SH-5 (10μmol/L) and L-NAME (100μmol/L), the proliferative effect was reduced by H-7, hypericin, PD98059 and LY294002, but not by SH-5 and L-NAME. · CONCLUSION: (R,R)-XY-10 and (S,S)-XY-10 can induce cell proliferation through MAPK and PI3K dependent pathway.