In order to investigate whether brain endothelial cells activation and/or damage could be selectively monitorized, soluble vascular cell adhesion molecule 1 (sVCAM-1) and thrombomodulin (TM) levels were studied in serum and cerebrospinal fluid (CSF) of 39 multiple sclerosis (MS) patients in various phases of the disease, 19 patients with other non-inflammatory neurological diseases (OND) and 15 patients with inflammatory neurological diseases (IND). No differences in sVCAM-1 CSF levels were detected, except for lower levels in IND compared to OND. Serum TM levels were lower in IND compared to progressive MS patients. Moreover, a significant decrease both in VCAM index and in TM index was detected in IND compared to all other groups. TM index was higher in MS patients in progression as compared to OND. The combined analysis of sVCAM-1 and TM might be a useful tool in monitoring brain endothelium activation or damage in different phases of MS.