Introduction: Macrophages/microglial cells are considered as immune cells in the central nervous system. Interleukin (IL)-16 is a proinflammatory cytokine produced by activated monocytic cells. Materials and Methods: Expression of IL-16 was analyzed by immunohistochemistry in human astrocytic brain tumors and the rat C6 glioblastoma tumor model. IL-16 was detected in both human astrocytic brain tumors and rat C6 glioma. Results: Compared with human control brains, a significant increase in the percentages of parenchymal IL-16+ macrophages/microglia was observed already in grade II astrocytomas, indicating that IL-16+ immunostaining could be a descriptor of a macrophage/microglia subset in astrocytic brain tumors. A further increase was observed at the transition from grade II to III astrocytomas. This increase in IL-16 immunoreactivity correlated with WHO grades of human astrocytic brain tumors. Conclusions: Therefore, IL-16 might be a so far unknown factor in the regulation of the local inflammatory milieu of human and experimental astrocytomas.