Aim To investigate the effect of calcitonin gene-related peptide (CGRP) on the proliferation and energy metabolism of vascular smooth muscle cells(VSMC) induced by angiotensin Ⅱ (AngⅡ),and further explore whether AMP-activated protein kinase (AMPK) involved in the cellular signal pathway. Methods VSMC were prepared from thoracic aorta of male Sprague-Dawley rat by the explanted method. The 3 ~ 10 passages of cells were used for the present studies. The viability of cultured VSMC was estimated by MTT assay and cells counting. Cellular energy metabolism was tested by ATP assay kit,Janus Green B staining. Western Blotting was used to observe the expressions of phospho-AMPK (p-AMPK) in VSMC. Results AngⅡ (100 nmol/L) increased the viability of VSMC. Pretreatment of the cell with CGRP significantly inhibited VSMC proliferation,hypertrophy of mitochondria,extra-generation of ATP induced by AngⅡ (P<0.05). Meanwhile,CGRP down-regulated expressions of p-AMPK induced by AngⅡ,which were partly abolished by CGRP8-37 or PD98059,respectively. Conclusion Pretreatment with CGRP inhibits the proliferation and energy metabolism of VSMC induced by AngⅡ. The signal transduction involving in this process is likely to be related with the signal linkage,namely,CGRP/CGRP receptor-1(CGRPR-1)-mitogen extracellular kinase (MEK)/ ERK1/2-p-AMPK.