Objective OxLDL can increase Plin2 expression, then promote the formation of foam cells. LOX1 was a scavenger receptor for oxLDL. Here, we investigate the relationship between Plin2 and LOX1 in the progress of atherosclerosis.Methods The data GSE43292 from GEO database were analyzed for Plin2 and LOX1 expressions and the correlation between Plin2, LOX1 and NF-κB pathway. RAW264.7 cells stimulated by oxLDL served as a cellular model of atherosclerosis. The Plin2, LOX1 and p-p65 expressions were analyzed by immunoblotting, the intracellular lipids were detected by BODIPY 493/503 staining.Results The Plin2 and LOX1 expressions in atheroma plaques were significantly higher than that in adjacent carotid tissues by analyzing GSE43292. The expressions of Plin2 and LOX1, the lipid droplets were increased obviously in RAW264.7 cells after treated with oxLDL for 24 h. And Plin2 overexpression significantly increased the expression of LOX1. This change was more obvious after oxLDL incubation. But knockdown Plin2 maked no difference on LOX1 when without oxLDL treatment. Furthermore, the GSEA plot showed that the expressions of Plin2 and LOX1 were positively related with NF-κB activation in atherosclerosis. Meanwhile, although oxLDL incubation, NF-κB inhibitor JSH-23 pretreatment significantly reduced Plin2 and LOX1 expressions and the amounts of intracellular lipids. In addition, the expressions of Plin2 and LOX1 were significantly inhibited by JSH-23 in spite of Plin2 overexpression plus oxLDL incubation.Conclusion Altogether, Plin2 can promote the intracellular lipids accumulation and may participate in pathophysiological process of atherosclerosis by increasing the expression of LOX1, which at least partly through the activation of NF-κB pathway.