Neuregulin receptor degradation protein-1 (Nrdp1), a kind of ring finger E3 ubiquitin ligase, is expressed in several adult tissues, including the heart, testis, prostate and brain. Studies of this molecule have demonstrated its great importance in regulating cell growth, apoptosis and oxidative stress in various cell types. However, information regarding its expression and possible function in the central nervous system is still limited. In this study, we performed a neuroinflammation model by lipopolysaccharide (LPS) lateral ventral injection in adult rats. It was found that the expression of Nrdp1 was significantly increased in cerebral cortex after LPS injection. Immunofluorescence indicated that Nrdp1 was located in the neurons, but not astrocytes or microglia. Furthermore, there was a concomitant up-regulation of active caspase-3 and decreased expression of BRUCE (an inhibitor of apoptosis protein). In addition, decreasing Nrdp1 levels by RNA interference in cortical primary neurons reduced active caspase-3 expression but induced up-regulation of BRUCE. Collectively, all these results suggested that Nrdp1 might play a role in neuronal apoptosis by reducing the expression of BRUCE in neuroinflammation after LPS injection.