Ecto-nucleotide pyrophosphatases/phosphodiesterases (E-NPPs) are membrane-bound ecto-enzymes involved in the modulation of purinergic signaling. Important physiological roles related to brain development have been associated to purinergic neurotransmission. NPP1, two splice isoforms of NPP2, and NPP3 have already been identified in adult rat brain. However, there are no studies evaluating the mRNA expression of these NPP members during the brain development. The effort of the present study was to map NPP gene expression pattern in olfactory bulb, hippocampus, cerebral cortex, striatum, and cerebellum at crucial ages for rat development (7, 14, 21, 60, and 150 days old) by a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) strategy. Our results demonstrated an increase in the relative expression of NPP1 throughout the aging in all structures analyzed, except in hippocampus, where the higher expression has been detected in 14 days old rats. Both NPP2 isoforms have shown a similar pattern of expression among all structures. The relative expression of NPP3 decreased during the aging mainly on cerebellum, hippocampus, and olfactory bulb. Altogether, the different patterns of NPP gene expression during rat brain development reinforce the idea that each enzyme may play a distinct role on modulating the purinergic signaling throughout aging.