In rats, it is sometimes difficult to distinguish malignant reticuloses from astrocytomas in routine histopathological assessment. In the present study, four spontaneous brain neoplasms developing in the cerebrum of one Wistar Hannover rat and three Sprague-Dawley rats were immunohistochemically examined using microglia and macrophage markers. Histopathologically, these neoplasms were localized mainly in the cerebral cortex, hypothalamus or piriform lobe, and the portions showing solid growth did not show characteristic cellular arrangement but had an indistinct boundary with the surrounding brain parenchyma. Neoplastic cells had oval or pleomorphic small nuclei with abundant eosinophilic cytoplasm. Two cases showed neoplastic cell infiltration into the meninges and perivascular spaces. Silver staining showed lack of reticulin fiber production in the stroma of the neoplasms. Immunohistochemically, the neoplastic cells were strongly positive for Iba-1 and sporadically positive for CD68 in all four cases. On the basis of these results, all the neoplasms examined here could be distinguished from astrocytomas and diagnosed as malignant reticuloses. Thus, immunohistochemical demonstration of microglia/macrophage characters, such as using Iba-1, is considered to be helpful for differential diagnosis of malignant reticuloses from astrocytomas among spontaneously occurring primary brain neoplasms in rats.