Abstract: AIM To investigate the effect of atorvastatin on 7-ketocholesterol (7-KC)-induced endoplasmic reticulum stress (ER stress) and apoptosis in macrophages. METHODS We generated an ApoE-/- mouse model of vulnerable carotid atherosclerotic plaque by partial ligation of the left common carotid artery and left renal artery. The pathological changes of atherosclerotic plaques were observed by hematoxylin-eosin (HE) staining and the expression level or phosphorylation status of ER stress-associated proteins (CHOP and p-PERK) were detected by immunofluorescence staining. Macrophages (murine RAW 264.7 cells) were cultured and incubated with 7-KC or H2O2 with or without pretreatment with atorvastatin. ER stress-associated proteins (CHOP, p-PERK, XBP-1s) and apoptotic protein (cleaved caspase-3) were measured by Western blotting. RESULTS Vulnerable carotid atherosclerotic plaques from ApoE-/- mice showed induction of ER stress, as indicated by elevated CHOP levels and PERK phosphorylation. Levels of CHOP expression, PERK phosphorylation and cleavage of caspase-3 were elevated after exposure RAW264.7 cells to 7-KC, as well as to the direct inducer of oxidative stress H2O2. Atorvastatin inhibited 7-KC- and H2O2-induced ER stress and apoptosis in RAW264.7 cells in vitro. CONCLUSION 7-KC and oxidative stress induce ER stress and apoptosis in macrophages in vulnerable atherosclerotic plaques. Atorvastatin inhibits ER stress and apoptosisvia reducing oxidative stress.