Objective To explore the effects of Total Flavonoids from Litchi Seed on the expression of differential lncRNAs and mRNAs in liver fibrosis rats using high-throughput sequencing technology and to analyze its biological func-tions.Methods Experiments was conducted at the experimental animal center of Guangxi University of Chinese Medicine from April 2021 to July 2021.A rat model of liver fibrosis was established,with rats randomly assigned to the control group(Control),model group(Model),and Total Flavonoids from Litchi Seed group(TFL).The TFL group was administered 50mg·kg-1·d-1 of TFL for a total of 6 weeks.HE and Masson staining were used to observe liver tissue fibrosis chan-ges.Serum levels of hyaluronidase(HA),type Ⅳ collagen(Ⅳ-C),laminin(LN),and type Ⅲ procollagen(PC Ⅲ)were meas-ured using ELISA.RNA-seq high-throughput sequencing technology was used to identify differentially expressed lncRNAs and mRNAs between the Model and TFL groups.The cis method was used to predict target genes of differentially ex-pressed lncRNAs.GO and KEGG analyses were conducted for biological function enrichment of the differentially expressed lncRNAs target genes and mRNAs.Results Compared with the Model group,the TFL group exhibited a significant de-crease in liver fibrosis score(F=14.420,P<0.001)and serum levels of HA,Ⅳ-C,LN,and PC-Ⅲ(F=47.055,74.655,177.328,54.445,P<0.001).A total of 73 differentially expressed lncRNAs(43 up-regulated,30 down-regulated)were identified be-tween the Model and TFL groups,along with 261 differentially expressed mRNAs(150 up-regulated,111 down-regulated).Using the cis method,24 target genes were predicted between the Model and TFL groups.Biological function enrichment analysis indicated that TFL plays an anti-liver fibrosis role by participating in signaling pathways such as circadian rhythm,glutathione metabolism,ubiquinone,and pentose phosphate.Conclusion TFL significantly improved the pathological mor-phology of fibrotic tissue in rats,reduced serum levels of HA,Ⅳ-C,LN,and PC-Ⅲ,and exerted an anti-liver fibrosis effect.The mechanism of action may involve regulating the expression of specific differential lncRNAs and mRNAs and participat-ing in signaling pathways such as circadian rhythms,glutathione metabolism,ubiquinone,and pentose phosphate.