By histochemical and immunocytochemical techniques, this study aimed to determine the possible involvement of apoptosis in regulating the microglial distribution in fetal rat brain. While microglial cells were labeled with the isolectin Griffonia simplicifolia (GSA I-B4), apoptotic cells were detected by using terminal transferase-mediated dUTP nick end-labeling (TUNEL). TUNEL-labeled cells occurred mainly in the dorsal midline along its rostral-caudal axis of the brain where lectin-labeled microglia were also observed. Occasional TUNEL-labeled cells were observed in the intermediate zone lateral to the striatum (IZS) where lectin-labeled microglia were common from embryonic day 16 (E16) onwards. Some of lectin-labeled microglia showing different morphological forms ingested TUNEL-labeled bodies. In contrast, lectin-labeled microglia showing signs of apoptosis appeared to be lacking. These results clearly demonstrated that lectin-labeled microglia were distributed in areas with and without the occurrence of a large concentration of TUNEL-labeled cells. Our studies suggest that microglia in fetal rat brain will undergo differentiation and activation rather than apoptotic death to govern their population.