[Abstract] Objective: Based on the regulation of cholesterol reverse transport by Apoa-I, to explore the effect of phosphatidylcholine on hyperlipidemic mice. Method: Thirty Apoa-I -/- mice were randomly divided into Apoa-I -/- group, Apoa-I -/-+HFD group, and Apoa-I -/-+HFD+PC group using a random number table method; 30 C57BL/6J mice were randomly divided into WT group, WT+HFD group, and WT+HFD+PC group as a control group, with 10 mice in each group. The Apoa-I -/- group and WT group were fed with basic feed, while the other groups were fed with high-fat feed for 8 weeks to establish a hyperlipidemia model. Starting from the 9th week, the WT+HFD+PC group and Apoa-I -/-+HFD+PC group were given PC 2.5 g·kg-1·d-1, while the remaining mice were given physiological saline by gavage for a total of 4 weeks of intervention. The serum lipid levels of mice were detected using a fully automated analyzer. Hematoxylin eosin (HE)staining and Oil red O staining was used to observe pathological and morphological changes in mouse liver tissue. COD-PAP method was used to detect cholesterol levels in mouse liver tissue. ELISA method was used to detect LCTA levels in mouse serum RT-qPCR and Western Blot methods were used to detect the mRNA and protein expression of cholesterol ATP binding cassette transporter A1,（ABCA1）, ATP binding cassette transporter G1（ABCA1）, lecithin cholesterol acvltransferase（LCAT）, Hepaticlipase（HL）, scavenger receptor class B type I（SR-BⅠ）, low density lipoprotein receptor（LDL-R） in liver tissue. RESULTS: Compared with the WT group, the serum lipid levels of mice in the WT+HFD group were significantly increased (P<0.01), hepatic fat vacuoles were obvious, hepatic lipid deposition was significant, and TC levels in liver tissue were significantly increased (P<0.01). The mRNA and protein expressions of ABCA1, ABCG1, LCAT, SR-B1, HL, and LDL-R were significantly increased (P<0.05, P<0.01). Compared with the WT+HFD group, the serum lipid levels of mice in the WT+HFD+PC group were significantly reduced (P<0.05, P<0.01), hepatic fat vacuoles were significantly reduced, hepatic lipid deposition was alleviated, and TC levels in liver tissue were significantly reduced (P<0.01). The mRNA and protein expressions of ABCA1, LCAT, SR-B1, HL, and LDL-R were significantly reduced (P<0.05, P<0.01); The serum levels of TC, TG, and LDL-C were significantly increased in the Apoa-I -/-+HFD group mice, while the levels of HDL-C were significantly reduced (P<0.05, P<0.01). Hepatocytes underwent balloon like transformation, liver lipid deposition was significantly aggravated, and TC levels in liver tissue were significantly increased (P<0.05). The mRNA and protein expressions of ABCA1, LCAT, HL, and LDL-R were significantly increased (P<0.05, P<0.01). Compared with the WT+HFD+PC group, the Apoa-I -/-+HFD+PC group mice showed a significant increase in serum lipid levels (P<0.05, P<0.01), significant hepatic lipid vacuoles, significant hepatic lipid deposition, and a significant increase in TC levels in liver tissue (P<0.05). The mRNA and protein expressions of ABCA1, ABCG1, LCAT, SR-B1, and HL were also significantly increased (P<0.05, P<0.01). Conclusion: Phosphatidylcholine can improve dyslipidemia in hyperlipidemic mice by interfering with Apoa-I and then regulating cholesterol reverse transport.