Experimental autoimmune neuritis (EAN) is a well-known animal model of Guillain-BarrE Syndrome. In this study, we studied the spatiotemporal expression of interleukin-16 (IL-16) in the nervous system of EAN rats and pharmacological effects of minocycline on IL-16 expressions in EAN rats. In sciatic nerves and dorsal/ventral roots of EAN rats, IL-16(+) cells, identified as macrophages and T cells, were mainly found to concentrate around blood vessels. However, in spinal cords, IL-16(+) microglial cells were mainly found in lumbar dorsal horns. Massive IL-16(+) cell accumulation in sciatic nerves and spinal roots was temporally correlated with severity of neurological signs of EAN. Furthermore, a strong correlation of IL-16(+) cell accumulation with local demyelination in perivascular areas of sciatic nerves, and significant reduction of IL-16(+) cell numbers in sciatic nerves and spinal cords by minocycline suggested a pathological contribution of IL-16(+) cells in EAN. Taken together, robust IL-16(+) cell accumulation in the nervous system and its temporal correlation with severity of neurological signs in EAN might suggest a pathological role of IL-16 in EAN, which makes IL-16 a potential pharmacological target.