Objective: In this study, we investigated matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMPs) in cerebrospinal fluid (CSF) and plasma of traumatic brain injury (TBI) patients. Patients and Methods: A total of 30 patients with moderate and severe TBI and 15 age-matched controls were enrolled in this study. Plasma and CSF samples were collected within 24 h (as the initial value), at 72 and 120 h post injury. CSF and plasma MMP-9, MMP-2, TIMP-1 and TIMP-2 were estimated using ELISA. Different levels of these indexes were compared in the two groups and further investigated the correlation between each other. Results: There was a significant elevation in the levels of the initial MMP-9 in the CSF (P < 0.05), which lasted for 72 h post injury. TIMP-1 kept increasing within 120 h post injury and it was different compared with TIMP-1 at 24 and 72 h post injury. Plasma levels of MMP-9, MMP-2, TIMP-1 and TIMP-2 in TBI patients were also significantly different from those in controls. Furthermore the CSF MMP-9 in patients with severe TBI was higher than that in patients with moderate TBI. In addition, there was a positive relationship between the initial MMP-9 and TIMP-1 at 120 h post injury (r = 0.614, P < 0.01). Conclusion: MMPs and TIMPs are increased in both CSF and plasma of TBI patients. TIMP-1 has a positive correlation with MMP-9 and the initial MMP-9 is associated with the neurological outcomes.