PURPOSE: Astragalus polysaccharide (APS), a water-soluble heteropolysaccharide, possesses immunomodulatory, anti-inflammatory, and cardioprotective properties. This study investigates the neuroprotective potential of APS in a model of METHODS: Retinal function was evaluated using electroretinography (ERG), optomotor reflex (OMR), and flash visual evoked potentials (FVEP). Retinal inflammatory responses were examined through immunohistochemistry, western blotting (WB), and quantitative reverse transcription PCR (qRT-PCR). To assess the integrity of visual projections, an intravitreal injection of adeno-associated virus (AAV) was employed to trace the projections of retinal ganglion cells (RGCs) to the visual centers. RESULTS: APS treatment conferred protection to retinal cells, as indicated by ERG and OMR assessments. And APS intervention mitigated NMDA-induced apoptosis, evidenced by a decrease in TUNEL-positive cells. Furthermore, APS treatment attenuated the NMDA-induced reduction in RGC projections to the visual centers, including the superior colliculus and lateral geniculate nucleus, as demonstrated by AAV tracing. CONCLUSIONS: Our findings reveal that APS shields the retina from NMDA-induced damage by inhibiting the NF-κB signaling pathway and reduces the detrimental effects of NMDA on RGC projections to the visual centers. These findings propose APS as a potential novel therapeutic agent for the treatment of retinal diseases.