We use intracisternal (i.c.) injection of fluorescent-superparamagnetic iron oxide nanoparticles (SPION) in SIV-infected monkeys that labeled CNS CD68-CD163-CD206 perivascular, meningeal, and choroid plexus (CP) macrophages. SPION + CD163 + macrophages are also found in the optic nerves, nasal septum, and cribriform plate - potential sites-paths of macrophage exit. Outside the CNS CD163 + SPION + macrophages labeled in the CNS are in deep cervical lymph node (dCLN), spleen, dorsal root ganglia (DRG). CD163 + SPION + CNS macrophages are abundant 24 hours p.i. in normal animals and decrease over time without CNS inflammation, but accumulate with SIV infection and inflammation. Greater numbers of SPION + macrophages traffic out of the CNS in normal animals and decrease with infection. Productively infected, SPION + macrophages are found in the CNS and dCLN, spleen, and DRG of infected animals 7-14 days post i.c. injection. These data are consistent with SPION + macrophages, some of which are viral infected, trafficking out of the CNS.