AIM:To determine the involvement of the interleukin (IL)-6 with the development of experimental subretinal fibrosis in a mouse model.METHODS:Subretinal fibrosis was induced by subretinal injection of macrophage-rich peritoneal exudate cells and the local expression of IL-6 was assessed by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) at various time points. In addition, we investigated the effect of IL-6 receptor (IL-6R) monoclonal antibody (MR16-1) on subretinal fibrosis development.RESULTS:IL-6 mRNA level was significantly elevated at 1d after subretinal fibrosis induction and increased further to about 12-fold at 2d, reaching the peak. The result of ELISA showed that IL-6 protein was not detected in naive mice. At 2d after subretinal fibrosis induction, IL-6 protein level was upregulated to 67.33±14.96 pg/mg in subretinal fibrosis mice. MR16-1 treatment resulted in a reduced subretinal fibrosis area by 48% compared to animals from control group at 7d.CONCLUSION:Our results indicated that IL-6 signaling may contribute to the pathogenesis of subretinal fibrogenesis and IL-6R inhibition may provide an effective, novel treatment of advanced and late-stage neovascular age-related macular degeneration.