The pancreatitis-associated protein (PAP) family is a group of 16-kDa secretory proteins initially identified in the pancreas in rats with acute pancreatitis. Although induction of PAP family genes was reported in peripheral nerve injury models, the expression in the central nervous system after traumatic injury has not been examined. In the present study, we examined the expression of PAP family members (PAP-I, PAP-II, and PAP-III) in the rat brain following traumatic brain injury (TBI) induced by weight drop. There was a significant upregulation of PAP-I and PAP-III mRNA in the injured cortex beginning at 1 day after TBI. Immunohistochemical double-staining indicated that PAP-I and PAP-III staining was localized in a subpopulation of neurons in the peri-injured region. Expression of both PAP-I and PAP-III mRNA was observed following a transient increase in inflammatory cytokines, including TNF-alpha, IL-6, and IL-1beta mRNA. The results of the present study suggest that expression of PAP family members in response to traumatic and inflammatory stimuli are not restricted to the pancreas, intestine, and peripheral nervous system, and are likely a more general cellular response, including the central nervous system in the rat. Thus, PAP family members may have an anti-inflammatory role, and this may contribute to the protection of injured neurons.