Abstract: Objective: To prepare TG-DHA liposome and investigate its effect on the expression of appetite regulating factors in high fat diet-fed mice. Methods: Firstly, TG-DHA liposomes were prepared by thin film dispersion method. Subsequently, C57BL/6J mice were housed and randomly divided into control group (C), model group (M), and TG-DHA liposome group (L-DHA). The gavage dose was 1000 mg/kg.bw. After 8 weeks gavage, Serum leptin, insulin and proopiomelanocortin (POMC) were detected using ELISA; The mRNA expression of neuropeptide Y (NPY) 、α-melanocyte stimulating hormone (α-MSH) 、cholecystokinin (CCK)、peptide YY (PYY) and glucagon like peptide-1 (GLP-1) were determined using RT-PCR method. Results: The encapsulation efficiency of TG-DHA liposomes was 85.83%. Compared with the M group, the L-DHA group significantly improved the content of serum leptin (23.03%) and POMC (1.30) (P<0.01), and the mRNA expression levels of α-MSH (1.60)、PYY (1.32) and GLP-1 (78.10%) (P<0.05). Conclusion: TG-DHA liposome could improve the abnormal expression of appetite regulating factors such as serum appetite hormones, hypothalamic neuropeptides and brain-gut peptides, inhibit the appetite of high-fat diet mice, thereby improving obesity induced by high-fat diet.