Objective To establish a mouse model of retinal inflammation induced by the intravitreal injection of amyloid β (Aβ), a major component in drusen. Methods This was an experimental study in C57BL/6J mice to determine the optimal concentration of Aβ1-40, the mRNA expressions of inflammatory cytokines interleukin-6 (IL-6), the tumor necrosis factor-α (TNF-α) and nucleotide-binding oligomerization domain leucine-rich repeats containing pyrin domain 3 (NLRP3) inflammasome were examined at 24 hours after the intravitreal injection of 2 µl of PBS or different concentrations (0.5, 1.0, 1.5, 2.0 µg/µl) of Aβ1-40. After determination of the concentration, mice were injected with optimal concentrations of Aβ1-40 (n=12) or Aβ40-1 (n=12) and the eyeballs were enucleated at days 1, 4 and 14 postinjection. The expression of inflammatory cytokines and the activation of NLRP3 inflammasome in the neuroretina and the RPE/choroid complex were analyzed by real-time PCR. The severity of retinal damage was evaluated with HE staining at day 4 postinjection (n=3 for each group), and retinal functions were evaluated by ERG at days 4 and 14 (n=12 in PBS group, n=8 in Aβ40-1 group and Aβ1-40 group). Differences between groups were analyzed using ANOVA followed by a post hoc Bonferroni correction. Results The optimal concentration of Aβ1-40 that could induce retinal inflammation was 1.0 µg/µl. Compared with Aβ40-1, Aβ1-40 significantly upregulated the expressions of IL-6, TNF-α and NLRP3 inflammasome genes in the neuroretina and the RPE/choroid complex at days 1 and 4 postinjection. The differences in inflammatory cytokine gene expression between these groups were not significant at day 14, except for the TNF-α in the neuroretina group. No structural disorganization or inflammatory cell infiltration was observed in the retina in each group under light microscopy at day 4. At days 4 and 14 after intravitreal injection, the amplitudes of ERG a- and b-waves significantly decreased in the Aβ1-40 injected mice compared to the untreated and the Aβ40-1 injected mice. No significant differences were observed between the untreated and Aβ40-1 groups at day 14, except for the amplitudes of the dark-adapted ERG b-wave recorded with light intensities of 1.0 and 10.0 cd·s/m2. Conclusion Our data show that Aβ1-40 induces a transient proinflammatory response in the neuroretina and the RPE/choroid complex, and causes retinal functional impairment. These responses mimic those observed in the early stages of age-related macular degeneration (AMD) patients. We find inflammasome is activated in this process. This novel model is useful for investigating the pathogeneses of early AMD.