Primary objective: Oxidative stress is the principal factor in traumatic brain injury (TBI) that initiates the events that result in protracted neuronal dysfunction and remodeling. Importantly, antioxidants can protect the brain against oxidative damage and modulate the capacity of the brain to cope with synaptic dysfunction and cognitive impairment. Research design: To date, however, no studies have investigated the effects of procyanidins (PC) on cognitive deficits after TBI. Methods and Procedures: In the present study, rats with controlled cortical impact (CCI) were used to investigate the protective effects of procyanidins. Main outcomes and results: The results showed that procyanidins reduced the level of malondialdehyde (MDA) and elevated the level of glutathione (GSH) and the activity of superoxide dismutase (SOD). In addition, treatment with procyanidins, which elevated the levels of brain-derived neurotropic factor (BDNF), phosphorylation-cAMP-response element binding protein (pCREB), total CREB, and cyclic AMP (cAMP), improved cognitive performance in the Morris water maze after TBI. Conclusions: These results suggest that procyanidins appear to counteract oxidative damage and behavioral dysfunction after TBI through antioxidant activity and the up-regulation of cAMP/CREB signaling.