OBJECTIVE: To investigate the trend of dynamic changes and the mechanisms of P2X7R by which berberine (BBR) alleviates chronic retinal light injury in mice. METHODS: A total of 90 mice were randomly divided into three groups, a blank control group ( RESULTS: Compared with the blank control group, the LD group exhibited abnormal retinal morphology, with some ganglion cells displaying reduced nuclei, a deeper stain, and loose arrangement. In the LD group, the cells in the inner nuclear layer appeared to be slightly more loosely arranged, while the cells in the outer nuclear layer cells were arranged in a disorderly way. Furthermore, the thickness of the outer nuclear layer of the retina from mice in the LD group was (47.11 ± 2.01) μm, and a significant number of apoptotic cells were observed in the outer nuclear layer, resulting in an apoptosis rate of (71.16 ± 5.99)% ( CONCLUSION: Berberine can alleviate chronic retinal photodamage in mice, and inhibit the activation of P2X7R, thereby preventing the formation of retinal photodamage.