Neuroinflammation, marked by the release of pro-inflammatory cytokines and resulting neuronal death, is a multifaceted process extending beyond traditional inflammatory pathways. Microglia, primary cells in the inflammatory response, rapidly activate during neuroinflammation and produce pro-inflammatory and cytotoxic factors that affect neuronal function. Recent evidence highlights the significant role of abnormal lipid droplet (LD) deposition in the pathogenesis of neuroinflammation. While microglia are known to influence LD aggregation during neuroinflammation, the regulatory mechanism within neurons is not well understood. Our study demonstrates that lipopolysaccharide (LPS)-activated microglia induce the accumulation of LD in neurons, identifying microglial-derived lactic acid as a key mediator in this process. Excessive lipid accumulation threatens neuronal function, a phenomenon reversed by eliminating microglia. These findings, corroborated in both in vitro and in vivo settings and supported by RNA sequencing, deepen our understanding of neuronal lipid metabolism and suggest potential targets for therapeutic strategies against acute neuroinflammation.