Background　The　side　effects　caused　by　Polygoni　Multiflori　Radix　(PMR)　and　Polygoni　Multiflori　Radix　Praeparata　(PMRP)　have　often　appeared　globally.　There　is　no　research　on　the　changes　of　endogenous　metabolites　among　PMR-　and　PMRP-treated　rats.　The　aim　of　this　study　was　to　evaluate　the　varying　metabolomic　effects　between　PMR-　and　PMRP-treated　rats.　We　tried　to　discover　relevant　differences　in　biomarkers　and　endogenous　metabolic　pathways.　Methods　Hematoxylin　and　eosin　staining　and　immunohistochemistry　staining　were　performed　to　find　pathological　changes.　Biochemical　indicators　were　also　measured,　one-way　analysis　of　variance　with　Dunnett＇s　multiple　comparison　test　was　used　for　biochemical　indicators　comparison　among　various　groups.　Metabolomics　analysis　based　on　ultra-high　performance　liquid　chromatography-quadrupole　time　of　flight　mass　spectrometry　(UPLC-Q/TOF-MS)　was　performed　to　find　the　changes　in　metabolic　biomarkers.　Multivariate　statistical　approaches　such　as　principal　component　analysis　(PCA)　and　orthogonal　partial　least　square-discriminant　analysis　(OPLS-DA)　were　applied　to　reveal　group　clustering　trend,　evaluate　and　maximize　the　discrimination　between　the　two　groups.　MetaboAnalyst　4.0　was　performed　to　find　and　confirm　the　pathways.　Results　PMR　extracts　exhibited　slight　hepatotoxic　effects　on　the　liver　by　increasing　aspartate　and　alanine　aminotransferase　levels.　Twenty-nine　metabolites　were　identified　as　biomarkers,　belonging　to　five　pathways,　including　alpha-linolenic　acid　metabolism,　taurine　and　hypotaurine　metabolism,　glycerophospholipid　metabolism,　arginine　and　proline　metabolism,　and　primary　bile　acid　biosynthesis.　Conclusion　This　study　provided　a　comprehensive　description　of　metabolomic　changes　between　PMR-　and　PMRP-treated　rats.　The　underlying　mechanisms　require　further　research.