Aim To study the effect of Dendrobium Huoshanense C.Z. Tang et S.J.Cheng(DH)on the development of atherosclerosis and vascular calcification induced by high-fat diet in LDLR－/－ mice and the possible mechanisms.Methods Male LDLR－/－ mice were randomly divided into 2 groups and received the following treatment:High-fat diet (control group); HFD containing DH (DH group). The treatment was lasted for 18 weeks. At the end of treatment, all the mice were anesthetized followed by collection of blood, aorta and liver samples. The serum was prepared followed by determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDLC) and low density lipoprotein cholesterol (LDLC) levels. Whole aorta and frozen cross sections of aortic root were prepared, and the lesions in en face aorta and aortic root cross sections were determined by oil red O staining. Frozen cross sections of aortic root were also stained by Sirius Red and Alizarin Red S to determine the plaque stability and vascular calcification. Liver frozen sections were prepared and used to determine hepatic lipid content by oil red O staining. Results After 18 weeks, DH lowered serum TG to (2.31±0.16) mmol/L compared to the control group (3.76±0.47) mmol/L(P＜0.05), but had no effect on transaminase level and otherlipid profilesin serum. Meanwhile, DH significantly reduced lesions in en face aorta and sinus lesion of aortic root by 20% (P＜0.05). It also increased collagen content by 70% in plaques (P＜0.05), promoted lesion stability and reduced necrotic cores in arterial wall. At last, Alizarin Red S staining showed that the development of vascular calcified area, which was 0.88% in DH group while 1.34% in control group, was attenuated by 34% (P＜0.01). Conclusion DH inhibits the development of atherosclerosis and vascular calcification.