Aim To determine the influence of testosterone and flutamide on atherosclerotic plaque stability and inflammatory reaction.Methods Pathological sections of aorta were performed with hematoxylin-eosin staining and Masson's trichrome staining.Total plasma testosterone was measured using Advia Centaur immunoassay system.The contents of serum tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) were assayed using radio-immunoassay kit.The concentrations of serum soluble intercellular adhesion molecule-1(sICAM-1) and matrix metallopeptidase-2(MMP-2) were assayed using enzyme linked immunosorbent assay(ELISA) kit according to the procedure described by the manufacturer.Results Testosterone undecanoate replacement reduced the plaque area and the aortic intimal thickness,and increased the fibrous cap thickness and collagen contents in castrated rabbits.However,presence of flutamide increased the plaque area and the aortic intimal thickness,and decreased the fibrous cap thickness and collagen contents in castrated rabbits again.Levels of serum TNF-α,IL-6,sICAM and MMP-2 increased in cholesterol-rich diet rabbits compared with standard diet rabbits.Castration caused an increase in levels of serum TNF-α,IL-6,sICAM and MMP-2 in castrated rabbits compared with sham-operated rabbits.Treatment of testosterone undecanoate reduced the levels of serum TNF-α,IL-6,sICAM and MMP-2 in castrated rabbits.However,presence of flutamide increased the levels of serum TNF-α,IL-6,sICAM and MMP-2 again.Conclusion Testosterone at physiological dose and flutamide can influence atherosclerotic plaque growth and stability and the levels of inflammatory factors.