Ｏｂｊｅｃｔｉｖｅ　To investigate the effect of methylprednisolone on markers of early vascular endothelial activation and damage after total knee arthroplasty.　Methods　We randomly selected 88 patients undergoing unilateral total knee arthroplasty. The patients were divided into two groups by a completely random grouping method(n=44), they were given either pre-operative intravenous methylprednisolone 120 mg (number of patients for methylprednisolone group) or isotonic saline (number of patients for control group). All operations were performed under lumbar spinal and epidural anesthesia. Blood samples were collected at 2, 6, 12 h and 24 h pre- and post-operation, respectively. By enzyme-linked immunosorbent assay(ELISA), we analyzed concentrations of Syndecan-1, plasma soluble thrombomodulin (sTM), E-selectin, vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) at different time points.　Results　There was no significant difference in age, gender, body mass index (BMI), operation time and ropivacaine dose between patients in two groups (P>0.05). Syndecan-1、E-selectin and CRP were significantly decreased at 2, 6, 12 h and 24 h in methylprednisolone group, sTM and VEGF were significantly decreased at 6, 12 h and 24 h in methylprednisolone group（P＜0.05）. Compared with preoperative, the level of Syndican-1 and E-selectin at 2, 6, 12 h and 24 h were significantly decreased, the level of CRP was significantly increased（P＜0.05）, the level of sTM and VEGF were significantly decreased at 6, 12 h and 24 h in methylprednisolone group （P＜0.05）.　Conclusions　Pre-operative administration of methylprednisolone 120 mg could reduce markers of endothelial activation, reduce the level of damage markers and reduce the systemic inflammatory response after total knee arthroplasty.