The proline-rich coiled coil 2B (prrc2b) is a conservative gene which is found in the genomes of most vertebrates. However, its function and expression pattern remains unknown. This study describes the spatio-temporal expression patterns of the PRRC2B protein in the rat brain with a view to inferring its function. The expression of PRRC2B protein was determined at embryonic day 18 (E18), postnatal day 1 (P1), postnatal day 7 (P7), postnatal day 15 (P15) and adulthood rats by Western blotting and immunohistochemical staining. Western blot results showed that the PRRC2B highly expressed in the whole brain tissues at E18, P1 and P7 but lowly expressed at P15 and adulthood. Immunohistochemical staining showed that the PRRC2B was located in the plasma and neurites of neurons with big size. The PRRC2B positive neurons widely distributed in most brain regions, including olfactory bulb, cerebral cortex, cerebellar cortex, hippocampus, thalamus, hypothalamus, superior colliculus, inferior colliculus, midbrain, pons and medulla oblongata, etc. Interestingly, there were obvious morphological differences between positive neurons in mature and immature rat brains. At P1 and P7 the protein highly expressed in the neuronic plasma, especially in the prominences and branches; while at P15 and adulthood, it only weakly expressed in the plasma. Above findings comprehensively revealed the expression pattern of PRRC2B protein in the whole rat brain at various stages for the first time, which should benefit to explore its function.