AIM: To explore the effect of immunization with copolymer-1 (COP-1) and retinal stem cells (RSCs) transplantation on interferon-gamma (IFN-γ) levels in a rat experimental glaucoma model. METHODS: An experimental glaucoma was induced by argon laser photocoagulation of the episcleral veins and limbal plexus in the right eye of rats. Immediately following glaucoma induction, rats were immunized with COP-1. RSCs were cultured and transplanted intravitreally into the eyes of glaucoma model animals 1 week post-laser treatment. Six experimental groups were used: COP-1/RSC, PBS/RSC, COP-1/PBS, PBS/PBS, glaucoma model group, and a normal control group. The concentration of IFN-γ in aqueous humor (AH) and serum was measured by enzyme-linked immunosorbent assay (ELISA) in each of the six groups. Retinal ganglion cell (RGC) survival was assessed by quantifying apoptosis using Hoechst staining. RESULTS: Concentrations of IFN-γ in AH and serum of rats that had undergone glaucoma induction were higher than those of non-induced control rats. The concentrations of IFN-γ in AH and serum of the COP-1/RSCs treated group were determined to be 2371.9ng/L and 710.9ng/L, respectively, which were significantly lower than those in the other treated groups (P<0.05). In fact, IFN-γ levels in the dual treated group were reduced to background levels. The COP-1/RSC group had lower number of apoptotic RGCs than the other three experimental groups (P<0.05). CONCLUSION: The reduced levels of IFN-γ in AH and serum of the COP-1/RSC group may be related to synergistic effects between RSCs transplantation and COP-1 immune modulation. It is likely that the lower levels of IFN-γ prevented RGCs glaucomatous apoptosis.