Aim To explore the effect of Pueraria Lobata Flowers Extract (PFE) on lipid accumulation in macrophage-derived foam cells. Methods The concentration of PFE in THP-1-derived foam cells was screened by MTT, intracellular lipid accumulation was detected by oil red O staining and cholesterol detection kit, intracellular cholesterol efflux levels were detected by cholesterol efflux assay kit, RT-qPCR and Western blot were used to analyze mRNA and protein expression. Results PFE significantly reduced lipid accumulation in THP-1-derived foam cells. PFE did not affect the mRNA expression of CD36, scavenger receptor-AⅠ (SR-AⅠ), sterol regulatory element-binding protein 2 (SREBP2), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), but it could upregulate the mRNA and protein expression levels of ATP-binding cassette transporter A1 (ABCA1) (P＜0.05), and promote the intracellular cholesterol efflux of macrophage-derived foam cells (P＜0.01). PFE could activate the activity of peroxisome proliferator-activated receptor γ (PPARγ) (P＜0.01) and upregulate the mRNA and protein expression levels of PPARγ (P＜0.05). Compared with the PFE control group, the expression of PPARγ and ABCA1 proteins decreased and cholesterol efflux decreased after GW9662 treatment (all P＜0.01). Conclusion PFE could significantly prevent the lipid accumulation in THP-1-derived foam cells and inhibit the formation of foam cells by upregulating ABCA1 expression and cholesterol efflux mediated by PPARγ.