Hyperlipidemia can be harmful to the pancreas and beta(3)-acirenoceptor agonist can improve lipid metabolism disorder. We aimed to study the effects of beta(3)-adrenoceptor activation on glucose, insulin and the expression of pancreatic adrenoceptors and angiotensin II receptors. Ten C57BL/6J mice at the age of 10 weeks served as normal control, and forty age-matched apolipoprotein E knockout (ApoE(-/-)) mice were randomly divided into hyperlipidaemia model group, low-dose and high-dose beta(3)-adrenoceptor agonist group and beta(3)-adrenoceptor antagonist group. After 26 weeks of high-fat diet, treatments were given for 12 weeks. Serum glucose and insulin levels in 48 weeks old mice were measured using an automatic biochemical detector. Quantitative rt-PCR and Western blot were used to analyze the mRNA and protein expression of alpha(1A)-, alpha(2A)-, beta(2)-, beta(3)-adrenoceptors and angiotensin II type 1 and type 2 receptors in pancreas. We found that beta(3)-adrenoceptor agonist could decrease serum glucose and insulin levels in aged ApoE(-/-) mice (P< 0.01) and down-regulate the expression of alpha(1A)-adrenoceptor and angiotensin II type 1 receptor which were significantly increased in model mice (P < 0.05, P < 0.01). Compared with the model mice, alpha(2A)-, beta(2)-, beta(3)-adrenoceptor and angiotensin II type 2 receptor expression were up-regulated in beta(3)-adrenoceptor agonist treat mice (P < 0.05, P < 0.01). These results suggest that chronic beta(3)-adrenoceptor activation regulated the expression of adrenoceptors and angiontensin II receptors towards contrary direction, which indicates that there are interactions between beta(3)-adrenoceptor and subtypes of adrenoceptor and angiotensin II receptor, and these interactions may play a protective role in pancreas and improve glucose metabolism disorders. (C) 2015 Published by Elsevier B.V.