Inflammation is one of the important contributing factors for the development of atherosclerosis and heart disease. Inflammation leads to the mobilization of various cells in developing atherosclerotic plaque and simultaneously triggers the up-regulation of various cytokine secretions from effector cells. To understand early molecular events during atherosclerosis we developed a rabbit model in which male New Zealand White rabbits were fed high cholesterol diets for 12 weeks. Total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C) and high sensitivity C-reactive protein (hs-CRP) were significantly increased in the high cholesterol diet group when compared to the control group during the experimental period (P<0.05). In parallel, the immunolocalization of CD40, MMP9, S100, CD68, α-smooth muscle actin and von Willebrand factor (vWF) in developing atherosclerotic plaque of the aorta and carotid artery was increased in comparison with the controls fed with a regular diet (P<0.05). From the present study, we conclude that a high cholesterol diet up-regulates CD68 and CD40, which may play a possible role in the remodelling and destabilization of the atherosclerotic plaque of arteries with the up-regulation of MMP9 and hsCRP. © 2009 Elsevier GmbH.