Apolipoprotein (Apo) E and ApoJ are lipid- and cholesterol-carriers in the central nervous system and are implicated in age-related neurodegenerative diseases. The primary source of secreted ApoE and ApoJ (clusterin) in the brain is glia. Regulation of these apolipoproteins in mixed glial cultures from rat cerebral cortex differed most strongly between neonatal- and adult-derived glia. Basal secretion of ApoJ was two-fold greater in neonatal than adult glia. Responses to cytokines also differed by donor age. In adult glia, IL-6 increased ApoE secretion, but slightly decreased ApoJ. Both IL-1 beta and TNFalpha treatments increased ApoJ secretion from adult glia, with little effect on ApoE. In contrast to adult glia, neonatal ApoJ secretion did not respond to IL-1 beta, IL-6, or TNFalpha, and ApoE secretion from neonatal glia was slightly increased by IL-6. These differences may contribute to age-related neuroinflammatory processes, and are pertinent to the general use of neonatal-derived primary glia in models for neurodegenerative disease.