Aim To investigate the effect of OX40-OX40L interaction on the expression of reactive oxygen species（ROS） and cyclophilin A（CyPA） in C57BL/6J mice. Methods Atherosclerotic plaque model was produced by rapid perivascular carotid collar placement in C57BL/6J mice. The expressions of CyPA in carotid atherosclerostic plaque and spleen lymphocytes were detected by immunohistochemical staining and Western Blot, respectively. The expressions of CD4, OX40 and the level of ROS were measured by flow cytometry. Results In vivo, the expression of OX40 in atherosclerotic C57BL/6J mice was significantly higher than that in non-atherosclerotic mice. And, the expression of ROS and CyPA in the lymphocytes of atherosclerotic mice were higher than those in control group （P<0.05）. In vitro, compared with control group, the expression of OX40 and the level of ROS were significantly increased in lymphocytes induced by anti-OX40. However, anti-OX40L significantly suppressed anti-OX40-induced up-regulation of OX40 and ROS in lymphocytes. The secretion of CyPA in stimulated group was more than that in inhibited group at 6 h （P<0.001）. Conclusion OX40-OX40L interactions can regulate the expression of ROS and CyPA in atherosclerotic mice.