Aim To investigate whether adipose differentiation-related proteins promote macrophage lipid accu-mulation by upregulating acyl-CoA synthetase long-chain family member 3(ACSL3)expression through PI3K/Akt.Methods The experiments were divided into 24 h group,different PLIN2 expression groups,HA-PLIN2+SC97 group and HA-PLIN2+LY294002 group.Western blot was used to detect the protein expression of PLIN2,Akt,p-Akt and ACSL3 in cells,RT-qPCR was used to detect the mRNA level of PLIN2 in cells,and oil red O was used to observe the degree of lipid accumulation in cells.Results The protein expression levels of Akt,p-Akt and ACSL3 in macrophages overex-pressing PLIN2 were significantly increased(P＜0.05),and p-Akt nuclear translocation was increased,with fluorescence labeling of PLIN2 and Akt overlapping.After adding the PI3K/Akt agonist SC97 to macrophages overexpressing PLIN2,the expression level of ACSL3 significantly increased(P＜0.05),and the degree of intracellular lipid accumulation in-creased;After adding the PI3K/Akt inhibitor LY294002 to macrophages overexpressing PLIN2,the expression level of AC-SL3 significantly decreased(P＜0.05),and the degree of intracellular lipid accumulation decreased.Conclusion PLIN2 upregulates ACSL3 expression through PI3K/Akt,thereby promoting macrophage lipid accumulation.