Abstract: AIM To investigate the effect and the molecular mechanism of cortistatin (CST) on rat aortic calcification. METHODS In vivo rat model of arterial calcification induced with vitamin D3 and nicotine (VDN), plasma calcium and calcium content of aortic tissue were determined by o-cresolphthalein complexion colorimetric method and von Kossa staining, respectively. Plasma phosphorus was measured by malachite green colorimetric method and calcification-related gene expression in aortic tissues was detected by RT-PCR. RESULTS Compared with those in the control group, VDN increased calcium content by 70.2% (P<0.05). Disorganized and broken elastic fibers were seen and von Kossa staining showed more positive brown/black particles in rat aortic tissues in VDN group. After chronic administration of CST 25 μg/kg, aortic calcium content was reduced by 45.6% (P<0.05) and disorganized elastic fibers and brown/black particles decreased in the VDN+CST group. No significant difference was observed in plasma calcium, phosphorus and calcium-phosphorus product between groups. Compared with those in the control group, expression of BMP-2 mRNA and Pit-1 mRNA increased by 53.2% (P<0.05) and 34.0% (P<0.01), respectively, and MGP mRNA expression decreased by 27.0% (P<0.05) in rat aortas in VDN group. After CST treatment, BMP-2 mRNA and Pit-1 mRNA expression were down-regulated by 38.3% (P<0.01) and 17.4% (P<0.05), respectively, and MGP mRNA expression increased by 34.9% (P<0.01) in aortic tissues of VDN+CST group compared with those in the VDN group. The amount of BMP-2 mRNA, Pit-1 mRNA and MGP mRNA expression showed no significant differences between control group and VDN+CST group. There was no significant difference in OPG mRNA expression of aortic tissue between groups. CONCLUSION CST alleviates rat arterial calcification induced by vitamin D3 and nicotine. Anticalcification of CST may be mediated by maintaining the expression homeostasis of calcification-related genes. These findings may provide some experimental evidence of using CST for the prevention and treatment of arterial calcification.