Aim To investigate the effect of Allicin on foam cell formation and atherosclerosis in ApoE－/－ mice fed with high-fat diet, and to further explore the possible molecular mechanisms. Methods 6-week ApoE－/－ mice were randomly divided into four groups:normal diet, high-fat diet, high-fat diet with low dose of Allicin, high-fat diet with high dose of Allicin. Total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDLC) and high density lipoprotein cholesterol (HDLC) were examined by a commercially available kit. Moreover, atherosclerotic plaque and foam cell formation were analyzed by oil red O, respectively. Further, the expression of SR-A and CD36 and the phosphorylation of JNK and p38 were determined by western blot. Results The level of TC, TG and LDLC in high-fat diet mice were dose-dependently decreased by Allicin(P<0.05). In addition, oil red O staining revealed that Allicin significantly inhibited the increase of atherosclerotic plaque and foam cell formation in high-fat diet mice(P<0.05). Furthermore, administration of Allicin markedly ameliorated high-fat diet induced increase of SR-A and CD36 expression and JNK and p38 phosphorylation in peritoneal macrophages(P<0.05). Conclusion Our findings demonstrate that Allicin ameliorates foam cell formation and atherosclerosis through inhibition of SR-A and CD36 expression and JNK and p38 phosphorylation.