In this study, an obese rat model induced by a high-fat diet (HFD) was used to investigate the modulating effect of 1-piperoylpiperidine (PIP) on circadian misalignment caused by metabolic dysregulation. The results showed that PIP attenuated HFD-induced liver injury, lowered blood lipid levels, alleviated circadian rhythm disruptionthe biological clock and lipid metabolism genes in the liver, and restored the changes in the expression of lysophosphatidic acid (16:0_18:1), bis-methyl phosphatidic acid (BisMePA, 38:8e), phosphatidyl ethanolamine (PE, 16:0p_22:6) and methylphosphocholine (MePC, 32:4e), which are closely associated with the biological clock. These findings may provide a theoretical basis for understanding the regulatory effect of PIP on the circadian rhythm of liver lipid metabolism.