Malignant peripheral trigeminal sheath tumor (MPNST) spreads to the brain parenchyma via the perivascular space (PVS). Nestin-expressing neoplastic cells lead tumor progression. Tumor-associated macrophages and microglia (TAMs) are a critical immune cells population for promoting this progression. In this work, we study the distribution of Nestin+ cells and TAMs in the infiltrative perivascular spaces of endogenous rat MPNSTs.MPNSTs are induced in Sprague Dawley rats by prenatal exposure of N-Ethyl N-nitrosourea (ENU). Tumor screening is performed by T1-w Magnetic Resonance Imaging and by immunoexpression of p53, Ki-67, NF, S-100, synaptophysin. PVS infiltrating cells are labelled by Nestin and BuChE markers. Microvessels and reactive microglia are observed by Lycopersicon esculentum lectin (LEA) histochemisty; TAM and astrocytes by Iba-1 and GFAP immunohistochemistry.ENU-MPNST develop in association with the fifth cranial nerve and proliferate through the interhemispheric cleft and Virchow-Robin spaces. TAMs account for about 15% of the neoplastic mass. In PVS, numerous BchE and Nestin+ cells are displayed adjacent to the astrocytic endfeet processes that conform the glia limitans. Some clusters of nestin+ cells break through this astrocyte barrier invading the brain parenchyma. These clusters are surrounded by numerous resident-microglial cells coexpressing LEA-Iba-1.The neoplastic cellular population expressing nestin and BchE drives the ENU-MPNST invasion of the brain parenchyma by overcoming the glia limitans. The microglial reaction is triggered in the areas surrounding the perivascular space where the infiltrating neoplastic cells are located. Therefore, these glial cells adjacent to the nestin cluster could play an essential role to prevent tumor progression.