Objective To investigate the influence of death receptor 5 (DR5) in the proliferation of nerve cells. Methods Totally 100 mice from embryonic day (E)16 to postnatal day (P)180 were used in the study, brain tissues were visualized for DR5 expression and the relationship between DR5 and neuroproliferation by immunohistochemistry of the bromodeoxyuridine (BrdU), DR5, doublecortin antibody from embryonic period to adult mice. Results In embryonic and newborn mice, the DR5 positive cells were distributed in granular layer densely with very strong fluorescence. After P7, the number of DR5 positive cells decreased, and the cells with intensive fluorescence were mainly located in subgranular layer, however, the rest of granular cells showed weak fluorescence. After P30, only a few DR5 positive cells were found in subgranular layer, and the granule cells appeared without fluorescence. Similar results were also observed in other proliferative zones, such as P0 cerebellum (external granular zone) and P7 rostral migratory stream of olfactory bulb. All the cells in those proliferative zones usually were DR5 positive with intensive fluorescence. Its developmental trend and distribution suggested the DR5 positive cells were proliferative cells or young postmitotic neurons. The further experiments also showed the DR5 positive cells in subgranular layer were double-stained with BrdU immunolabeling or doublecortin immunolabeling, demonstrating the DR5 positive neurons were neuroprogenitor cells and newborn postmitotic neurons. Conclusion The neuroprogentor cells and newborn neurons are usually DR5 positive cells, suggesting DR5 is involved in neuroproliferation and differentiation.