Background: Apelin is a cardiovascular peptide with multiple functions regulating homeostasis of the circulatory system and is the endogenous ligand of angiotensin receptor AT1 (APJ). The role of apelin/APJ system in vascular calcification (VC) was investigated here. Methods: Male Sprague-Dawley (SD) rats (200±10 g) were used. A rat aorta VC model was induced by vitamin D3 plus nicotine (VDN) in vivo, and cultured vascular smooth muscle cell (VSMC) calcification of rat thoracic aortic arteries was induced in vitro by beta-glycerophosphate [1, 2]. Rats anesthetized with urethane (1 g/kg, intraperitoneally) were killed. In aortic tissure or VSMCs, von Kossa staining, calcium content and alkaline phosphatase (ALP) activity was detected [1, 2]. Immunohistochemical assessment was used to detect alpha-actin. RT-PCR was used to detect mRNA expression of apelin and APJ, and Western blot was used to detect protein expression of apelin and alpha-actin. Results: Von Kossa staining revealed dispersed calcified nodules among the elastic fibres in calcified aortas but not in control aortas (n=6). As compared with controls, media from arteries with calcification showed significantly decreased level of alpha-actin on Western blot analysis (-18.4%, P<0.05, n=3, repeated three times). The mRNA relative level of apelin in the aorta of rats with vascular calcification was increased by 91.6% (P<0.05, n=3, reperated three times). However, the APJ mRNA expression have not significantly difference between two groups. To further investigate the effects of apelin, calcified VSMCs induced by beta-glycerophosphate were used. Compared with control group, protein expression of alpha-actin was significantly down-regulated in calcification group (P < 0.05, n=3, repeated three times). Calcium content and ALP acitivity increased by 109.6% and 83.7%, resprectively in calcification VSMCs (all P<0.05, n=6). Von Kossa staining showed dispersed calcified nodules in calcification group but not in control group (n=6). 10-9 mol/L apelin could further promote calcium content, ALP activity and calcified nodules than calcification alone (all P<0.05, n=6). However, 10-7 mol/L apelin ameliorated the calcified-induced augmentation of ALP activity (P< 0.05, n=6). Conclusions: These results suggest that apelin-APJ system might function as a regulator of VC, and could be new therapeutic targets for VC in patients.