Coptisine is one of main bioactive compounds extracted from the traditional Chinese herbal medicine Rhizoma Coptidis. It is reported that coptisine can attenuate obesity-related inflammation and oxidant damage in Syrian golden hamsters. Therefore，coptisine may exhibit beneficial effects for the treatment of atherosclerosis (AS) due to its hypolipidemic and anti-inflammation activities. The present study investigated the anti-atherosclerotic and anti-inflammatory properties of coptisine using apoE^−/− mice as AS model. The atherosclerotic plaque area of aorta, serum lipid profile and the expression of inflammatory cytokines were determined. After coptisine treatment, the serum level of TC, TG and LDL-C decreased; the serum level of IL-6, IL-1β and TNF-α were decreased; the mRNA levels of NF-κBp65, VCAM-1, ICAM-1, IL-6 and IL-1β in both aorta and liver were down-regulated; the p-p38 and p-JNK1/2 protein expression level were decreased. Coptisine decreased atherosclerotic plaque area significantly through both anti-inflammation and lipid lowering effect. The anti-inflammatory effect of coptisine is achieved through inhibiting activation of MAPK signaling pathways and NF-κB nuclear translocation. Therefore，the combined anti-inflammation and lipid lowering effect of coptisine attributed the decreased atherosclerotic plaque area in coptisine treated apoE^−/− mice. The results of this study will afford a novel application for coptisine in the treatment of atherosclerosis and other chronic inflammatory disease.