BACKGROUND: Animal studies have confirmed that hyperbaric oxygen (HBO) therapy can reduce matrix metalloproteinase activity and blood brain barrier permeability, thereby exhibiting neuroprotective effects. However, at present, consensus does not exist in terms of its clinical efficacy. OBJECTIVE: To validate the significance of changes in serum cellular adhesion molecule and MMP-9 levels in patients with cerebral infarction following HBO therapy. DESIGN, TIME AND SETTING: This randomized, controlled, neurobiochemical study was performed at the Department of Neurology, Affiliated Hospital of Qingdao University Medical College between December 2002 and March 2006. PARTICIPANTS: A total of 112 patients with acute cerebral infarction of internal carotid artery, comprising 64 males and 48 females, averaging (67 ± 11) years, were recruited and randomized to a HBO group (n = 50) and a routine treatment group (n = 62). An additional 30 gender- and age-matched normal subjects, consisting of 17 males and 13 females, averaging (63 ± 9) years, were enrolled as control subjects. METHODS: The routine treatment group received routine drug treatment and rehabilitation exercise. HBO treatment was additionally performed in the HBO group, once a day, for a total of 10 days. MAIN OUTCOME MEASURES: Serum levels of soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule, soluble E-selectin, and matrix metalloproteinase-9 were detected by enzyme linked immunosorbent assay. RESULTS: Upon admission, serum levels of soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule, soluble E-selectin, and matrix metalloproteinase-9 were significantly increased in patients with cerebral infarction, compared with control subjects (P < 0.01). Following HBO and routine treatments, serum levels of the above-mentioned indices were significantly reduced in the HBO and routine treatment groups (P < 0.01). Moreover, greater efficacy was observed in the HBO group, compared with the routine treatment group (P < 0.05 or P < 0.01). CONCLUSION: Intergroup comparison and case-control results indicated that HBO noticeably reduced serum levels of soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule, soluble E-selectin, and matrix metalloproteinase-9.