Paclitaxel, a well-known anti-cancer drug, hinders cell division by stabilizing microtubules. Despite its effectiveness, paclitaxel causes neuropathic pain, possibly due to its impact on the immune system. The study investigated how paclitaxel affects CP macrophages, important for the blood-cerebrospinal fluid barrier. It focused on two types of Kolmer cell macrophages in a model of paclitaxel-induced neuropathic pain. Wistar rats received either paclitaxel or its vehicle (Ethanol and chromophore). Brains, including those from naïve rats, were collected at different intervals (1, 7, 14, and 21 days) for immunohistochemical analysis. ED1, ED2, and Ki-67 antibodies were used to stain activated and resident Kolmer cells and CP cell proliferation. Results showed increased activated Kolmer cells in the CP after both paclitaxel and vehicle treatments, with no significant difference between the groups. Conversely, ED2 marker staining indicated more resident Kolmer cells after paclitaxel treatment. We also examined the colocalization patterns of Kolmer cells and proliferating cells under ED1 and ED2 conditions. However, we did not detect any proliferation of the resident and activated macrophages. Therefore, based on our findings, the Kolmer cells are possibly recruited rather than proliferate, so changes in their numbers may be influenced by alterations in the tight junctions present between the cuboidal cells. Our findings offer insights for enhancing paclitaxel's anti-cancer efficacy while minimizing potential immune-related side effects.