It is clear that activated beta(3)-adrenoceptor can improve disorders of lipid metabolism, however there are few reports concerning the anti-atherosclerotic effects of beta(3)-adrenoceptor in the artery of apolipoprotein E knockout (Apoe(-/-)) mice. In the present study, we aimed at investigating the effects of beta(3)-adrenoceptor On lipids, atherosclerosis plaques, scavenger receptor class B type 1 and its signal transduction in Apoe(-/-) mice. Ten C57BL/6J mice were used as a control, and fifty age-matched Apoe(-/-) mice were randomly divided into five groups: atherosclerotic model (saline), positive control (atorvastatin), low-dose beta(3)-adrenoceptor agonist, high-dose beta(3)-adrenoceptor agonist and beta(3)-adrenoceptor antagonist groups. After 26 weeks on the high-fat diet, the mice received the above treatments tot 12 weeks. Thoracic aortas, serum lipids, SR-B1, P-MeK1/2, P-ErK1/2 and protein kinase C alpha(PKC alpha) activity were detected. We found that the levels of serum total cholesterol, triglycericle, very low-density lipoprotein/low-density lipoprotein cholesterol and the area of atherosclerotic plaques were significantly decreased in beta(3)-adrenoceptor agonist-treated mice (P < 0.01), while the levels of high-density lipoprotein cholesterol, thoracic aortic lumen area, activity of liver PKC alpha, the protein expression of SR-B1, P-MeK1/2 and P-ErK1/2 were significantly increased (P < 0.01), compared with he atherosclerotic model mice. Effects of the high-dose agonist were superior to those of the low-close (P < 0.01). These findings suggest that activation of beta(3)-adrenoceptor reduce the plaque area in the thoracic aorta and play an important anti-atherosclerotic role by regulating lipid metabolism disorders and the SR-B1 signal transduction pathway. (C) 2013 Elsevier B.V. All rights reserved.