This investigation represents a pioneering effort to examine the therapeutic effects of PCB specifically in the context of CFA-induced mice, as well as to elucidate the underlying mechanisms that facilitate such effects. Our study utilized advanced methodologies, namely high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS)-based metabolomics, alongside comprehensive multivariate data analysis, to identify a distinctive metabolic profile associated with acute inflammation. Through our analyses, we discovered that several potential metabolites were significantly implicated in a variety of critical metabolic pathways. These pathways include glycerophospholipid metabolism, which plays an essential role in maintaining cellular membrane integrity and signaling; the biosynthesis of phenylalanine, tyrosine, and tryptophan, which are vital amino acids involved in numerous physiological processes; phenylalanine metabolism, which is significant for neurotransmitter synthesis; as well as the metabolism of alanine, aspartate, and glutamate, which are crucial for various metabolic functions, including neurotransmission and energy production. The metabolic alterations observed in both serum and spinal cord samples provide invaluable insights into the biochemical changes associated with inflammatory processes, thereby highlighting the potential therapeutic impact of PCB. The findings from this study not only deepen our understanding of the metabolic disturbances that occur during acute inflammation but also offer a solid theoretical foundation for clarifying the specific mechanisms through which PCB exerts its anti-inflammatory effects.