Abstract Background: Aquaporin 4 (AQP4) is the predominant water channel in the brain and is localized to the astrocytes and ependymal cells. In astrocytes it is expressed in the astrocyte membranes facing blood vessels and pia in a highly polarized manner. This polarization has been demonstrated to be important in the water and K+ homeostasis. Several studies indicate that the polarized expression of AQP4 has an important role in the pathophysiology of several cerebral disorders, including brain edema, epilepsy and Alzheimer s disease. Objective: In this study, we want to investigate the distribution and expression pattern of AQP4 in mouse substantia nigra (SN). AQP4 has not been explored in this area previously. By examining its distribution, we want to see whether AQP4 could have a role in the neuronal function in this area under normal and pathological conditions Methods: We investigated the AQP4 distribution in the SN and neocortex of C57BL/6 mice. The animals were perfusion fixed and brains analyzed using confocal immunofluorescence and quantitative immunogold electron microscopy. Results: We found significantly higher levels of AQP4 in the SN, as compared to the neocortex. The AQP4 expression was highly polarized around blood vessels, both in the pars compacta and pars reticulata. There was also substantially more AQP4 in astrocyte processes throughout the neuropil in the SN compared to the neocortex. Conclusion: The high expression of AQP4 in both endfeet and non-endfeet membranes indicate that this molecule might play an important role for maintenance of neuronal function in the SN. Studying expression pattern of AQP4 in mouse models of Parkinson s disease may give additional information about its functional significance.