OBJECTIVE: To investigate the protective effect of honokiol against the changes in the plexus choroideus tissue and the signaling. STUDY DESIGN: Rats were divided into 4 groups as control, honokiol, trauma, and trauma+honokiol groups. Traumatic brain injury was induced in Sprague-Dawley male rats (280–330 g) with a weight drop device using a 300 g/1 m weight-height impact. After 7 days of traumatic injury, blood samples were taken under ketamine hydroxide anesthesia and biochemical analyses were performed. The groups were compared in terms of biochemical values. Histopathological and immunohistochemical analyses were performed on tissue samples taken from the ventricular region. RESULTS: MDA and MPO values were high and GSH content was the lowest in the trauma group, but these values of honokiol treatment were close to those of the control group in the trauma+honokiol group. The increase in blood-brain barrier permeability was statistically significant in the trauma group as compared to the control and honokiol groups. Histopathological examination revealed degeneration in plexus epithelial cells, dilation and congestion in capillaries, increase in inflammatory cells around the basal membrane around the vessel, and increase in cerebrospinal fluid (CSF). Degeneration in cells was observed with honokiol treatment. It was observed that honokiol reduced inflammation and apoptotic effect. CONCLUSION: Honokiol, with its specific inhibitory effect on TNF-α protein, can effectively reduce inflammatory reactions. It was observed that it decreased the expression of APAF-1 and decreased the apoptosis of neurons. It was thought that it could regulate the plexus choroideus epithelial reorganization and CSF fluidity by improving the prognosis of motility dysfunction after traumatic brain injury. © Science Printers and Publishers, Inc.