Myopia is one of the major public health conditions with significant complications. This study investigates the role of transforming growth factor (TGF)-β2, complement activation, and inflammasome pathways in myopia progression using a Brown Norway rat model. Myopia was induced, and complement regulation was manipulated using gene therapy via adeno-associated virus (AAV) vectors delivering CD55 or CD55 siRNA. Results showed that TGF-β2 exacerbated myopia by upregulating complement components C3 and C5, suppressing CD55, and activating inflammasome pathways through nuclear factor (NF)-κB signaling, leading to axial elongation and increased refractive errors. Overexpression of CD55 via AAV gene therapy effectively counteracted these effects, reducing axial length elongation and inflammation by suppressing inflammasome markers interleukin (IL)-1β and NLR family pyrin domain containing 3 (NLRP3), as confirmed by real-time quantitative PCR and immunofluorescence analyses. Conversely, silencing CD55 intensified TGF-β2-induced effects, further promoting axial elongation and inflammation. These findings highlight the critical role of CD55 in modulating TGF-β2-driven complement and inflammasome activation during myopia progression. The study suggests that gene therapy targeting CD55 could serve as a novel therapeutic strategy to mitigate myopia and related inflammatory processes, offering a promising avenue for managing this significant public health challenge.