AMP-activated protein kinase (AMPK) plays a crucial role in governing essential cellular functions such as growth, proliferation, and survival. Previously, we observed increased vulnerability to bacterial (S. aureus) endophthalmitis in global AMPKα1 knockout (KO) mice. In this study, we investigated the specific involvement of AMPKα1 in myeloid cells using LysM Cre ; AMPKα1 fl mice. Our findings revealed that while endophthalmitis resolved in wild-type (WT) B6 mice, the severity of the disease progressively worsened in AMPKα1 deficient mice over time. Moreover, the intraocular bacterial load and inflammatory mediators (e.g., IL-1β, TNF-α, IL-6, and CXCL2) were markedly elevated in the LysM Cre ; AMPKα1 fl mice. Mechanistically, the deletion of AMPKα1 in myeloid cells skewed macrophage polarization toward the inflammatory M1 phenotype and impaired the phagocytic clearance of S. aureus by macrophages. Notably, transferring AMPKcompetent bone marrow from wild-type mice to AMPKα1 KO mice preserved retinal function and mitigated the severity of endophthalmitis. Overall, our study underscores the role of myeloid-specific AMPKα1 in promoting the resolution of inflammation in the eye during bacterial infection. Hence, therapeutic strategies aimed at restoring or enhancing AMPKα1 activity could improve visual outcomes in endophthalmitis and other ocular infections.