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Background: Retinitis pigmentosa (RP) refers to a group of progressive photoreceptor degenerative diseases. The activation of microglia has been reported to play an important role in the photoreceptor degeneration in RP retinal. Bujing Yishi tablets (BJYS), a Chinese herbal medicine, has been used to treat retinal diseases in China with desirable effect in improving visual function. However, the mechanisms underlying the efficacy of BJYS treatment in RP are not yet fully understood., Purpose: Based on the preliminary experiments, this study aimed to investigate the therapeutic mechanism involved in treating N-Methyl-N-Nitrosourea (MNU)-induced retinal degeneration of RP with BJYS., Methods: To explore the efficacy of BJYS, a rat experimental RP model was established through intraperitoneal injection of MNU (50 mg/kg). Two experiment was carried out. After the treatment, we conducted H&E, TUNEL, retinal cytokine levels and IBA-1 expression in microglia to confirm the impact on RP model. The specific mechanism of action of BJYS tablet was assessed by western blot, real-time polymerase chain reaction (RT-PCR), and immunofluorescence to determine the mRNA and protein expression levels involved in clarifying the effectiveness of BJYS exerted through P2X7R/CX3CL1/CX3CR1 pathway., Results: Significant alleviation of retinal morphological structure and photoreceptor degeneration by BJYS treatment was observed in the retinal of MNU-induced RP rats, BJYS prevented the reduction of ONL thickness and decreased the level of apoptotic cells in ONL. It also inhibited microglia overactivation and reduced retinal levels of IL-1β, IL-6, TNF-α. In addition, BJYS decreased the protein expression and mRNA expression of P2X7, CX3CL1 and CX3CR1 and reduced the phosphorylation of p38 MAPK., Conclusion: In summary, this study suggested that BJYS treatment could alleviate photoreceptors degeneration of RP by inhibiting microglia overactivation and inflammation through the P2X7R/CX3CL1/CX3CR1 pathway. These effects suggest that BJYS tablets may serve as a promising oral therapeutic agent for RP., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)