In multiple sclerosis (MS), a group of matrix metalloproteinases (MMPs) and their natural tissue inhibitors of metalloproteinases (TIMPs) may play a role in preventing tissue damage. The aim of this study was to determine the correlation between the MMP-9, MMP-2, TIMP- 1, and TIMP-2 serum levels and the possible relationship to the type, severity, and progressive course of MS. Eighty-nine patients and 22 healthy volunteers were enrolled in the study. The MS patients were grouped as follows: 35 relapsing-remitting patients with shortdisease- duration (RRMS-SDD) (≤5 years), 23 patients with longer-disease-duration (RRMSLDD) (≥10 years), 21 secondary progressive patients (SPMS), 6 progressive relapsing patients (PRMS) and 4 primary progressive patients (PPMS). Serum levels were analysed by ELISA. Compared with the Control Group, the TIMP-1 serum levels (ng/ml) increased [Group I (RRMS-SDD), 2242.2; Group II (RRMS-LDD), 3108.3; Group III (SPMS), 3108.3; Group IV (PRMS), 3552.3; Group V (PPMS), 2068.6; and Group VI (control group), 1554.9] (p<0.01), and the MMP-9/TIMP-1 ratios decreased [Group I, 0.074; Group II, 0.055; Group III, 0.043; Group IV, 0.028; Group V, 0.116; and Group VI, 0.107] (p<0.05) in all patient groups except the PPMS group. We re-classified the patients to reflect the progressive disease course as non-progressive (all RRMS) and progressive (PPMS, SPMS, and PRMS) groups. Compared with the control group, we again found an increase in TIMP-1 serum levels (ng/ml) [Groups I-II (RRMS=SDD and LDD), 2726.6; Groups III-IV-V (SPMS, PRMS, and PPMS), 3100.9; and Group VI (control group), 1554.9] (p<0.001) and a decrease in the MMP-9/TIMP-1 ratios [Groups I-II, 0.064; Groups III-IV-V, 0.046; and Group VI, 0.107] (p<0.01). In our study, the MMP-2, MMP-9, TIMP-2 serum levels and MMP- 2/TIMP-2 ratio were not significantly different between the groups altough reclassification. These results mirror the clinical stability that is related to the disease remission status of our patient sample. Further clinical trials will be necessary to examine potential drug targets to prevent patient attacks involving this dynamic pathophysiologic process of MS.