Aim To investigate the expression of Orai1 in the formation of atherosclerotic plaque of apolipoprotein E knockout （ApoE^－/－） mice. Methods 7 to 8 weeks old male ApoE^－/－ mice and wild-type C57BL/6J mice were selected and fed with fat rich diet. The animals were sacrificed consecutively after the mice were 20, 27 and 33 weeks old. Their aortas were taken for preparing the serial sections. The percentage of plaque area in luminal area was calculated after HE staining The percentage of collagen in plaque area was calculated after Masson staining Lipid content was analyzed after oil red O staining The percentage of smooth muscle cells expressing Orai1 was calculated after immunohistochemical staining. The dynamic expression of Orai1 during vulnerable plaque formation was quantitatively analyzed by using Western Blot analysis. Results Compared with the control group, the expression of Orai1 were markedly higher in ApoE^－/－ mice. As the age of ApoE^－/－ mice increasing, the expression of Orai1 increased significantly （P<0.05）. Conclusions Orai1 participates in the pathological process of atherosclerosis. The expression of Orai1 is up-regulated in the formation of atherosclerotic plaques.