Abstract: OBJECTIVE To investigate the mechanisam of minocycline on inflammation and atherosclerosis in ApoE^-/- mice. METHODS Eight-week old ApoE^-/- mice were assigned randomly into two groups: model group, minocycline (12 mg?kg^-1) and simvastatin group (5 mg?kg^-1). The mice were sacrificed after 12 weeks. The plasma total cholesterol, triglyceride, HDL and LDL concentration were measured. The lesion of atherosclerosis was observed pathological staining. Inflammatory cytokines were measured by real-time PCR. The plasma concentration of LTB4 and expression of 5-LOX was also measured by ELISA and Western blotting. RESULTS Minocycline signi?cantly ameliorated the formation of typical atheromatous lesions in ApoE^-/- mice, and reduced macrophage content in the atheromatous lesions of the aortic arch concomitant with upregulation the amount of collagen, which lead to stable atheromatous plaques. These ?ndings were supported by results showing that aortic MCP-1, IL-6, TNF-α, VCAM-1, MMP-2 and MMP-9 expression was decreased by minocycline. Minocycline also reduced the plasma concentration of LTB4 and aortic expression of 5-LOX. CONCLUSION Minocycline effectively attenuated atherosclerosis in mouse model, suggesting its therapeutic potential for atherosclerosis. The anti-atherogenic effect of minocycline might be associated with its inhibition on 5-LOX pathway.