To investigate the effects of glucose regulated proteins (GRP78 and GRP94) on brain development, the expression of GRP78 and GRP94 in brain during mouse development were examined by Western blot, Northern blot and immunofluorescence. The results showed that the GRP78 and GRP94 proteins were expressed in the different spatio-temporal patterns during brain development. The level of GRP78 was higher than GRP94 in embryonic brain during the early stages of organogenesis, and gradually decreased at the later fetal stages. In contrast, the level of GRP94 was gradually increasing and exceeded the level of GRP78 at later fetal stages. Furthermore, the level of GRP78 was gradually decreasing from telencephalon to hindbrain on E16.5 but GRP94 was not. As stress proteins, the levels of GRP78 and GRP94 in brain were similar during postnatal development of mouse. In addition, the distribution of GRP78 in brain was in agreement with GRP94, which was localized within the neurons and glial cells. These results suggested that GRP78 and GRP94 played the different roles in the process of nerve cell differentiation and brain morphogenesis. They had distinct functions in the different stages during brain development of mouse.