In our study, we investigated the possible mechanism and effect of celastrol on oxLDL-induced oxidative stress, foam cell formation and atherosclerosis in apolipoprotein E knockout (apoE−/−) mice fed with a high-fat/high-cholesterol diet (HFC) and whether the classical NF-κB signal pathway is involved in the antioxidative effect of celastrol. Here, APOE is linked to atherosclerosis.