Comparison of brain tissue water content (BWC) data with myeloperoxidase activity assay (MPO) allows for analysis of the complex pathophysiological mechanisms of cerebral edema following catastrophic brain injuries. The neuroprotective effect of an experimental anti inflammatory drug (FL1003, butyrolactone) was tested in a traumatic brain injury (TBI) model using BWC and MPO analysis. We conducted these studies on a mini-pig model of severe TBI that is well characterized in our laboratory. The animals were divided into three animal groups: no injury, no treatment (control), injured and treated with FL1003, and injured, untreated with FL1003. They were maintained with fluids for 24 hours under general anesthesia. We employed the MPO assay to identify the degree of inflammatory cellular response (polymorphonuclear leukocytes, PMNLs) 24 hours following TBI and calculated brain density from the data of the gravimetric (Percoll) column method for BWC on brain samples. Our results demonstrated increased infiltration of PMNLs and a shift of water into the extravascular space in the injured animals. These changes were significantly (P < 0.05) attenuated in the animal group treated with FL1003.