We studied behavioral and histological changes after fluid percussion brain injury and the effects of indeloxazine hydrochloride, a cerebral activator, on these post-traumatic changes in rats. An acquisition trial in passive avoidance task was conducted on the 3rd day after injury. The latency of step-through in injured rats was significantly (p < 0.05) shorter than that in sham-operated rats on the 4th, 10th and 14th days after the operation. There were injury-induced neurological deficits on days 1-4 post-injury. Histological changes were observed in the peripheral area of the cortical lesion at the impact site and in the thalamus but not in the hippocampus on the 14th day. Indeloxazine (10 and 20 mg/kg, p.o.) administered once a day from the 3rd (30 min prior to the acquisition trial) to the 9th day after injury significantly (p < 0.05) improved the impairment of the passive avoidance performance without affecting locomotor activity. Indeloxazine showed no significant effects on either neurological deficits or the cortical lesion area. These results suggest that impairment of passive avoidance performance occurs without apparent histological damage in the hippocampus after fluid percussion brain injury and is attenuated by post-traumatic treatment with indeloxazine.