Limited evidence suggests that brain cytosolic phospholipase A2 (cPLA2), which selectively releases arachidonic acid (AA) from membrane phospholipids, and cyclooxygenase-2 (COX-2), the rate-limiting enzyme for AA metabolism to prostanoids, change as a function of normal aging. In this study, we examined the protein levels of cPLA2 and COX-2 enzymes in hippocampus, frontal pole and cerebellum from young (2–5 year-old), middle-aged (8–11 year-old) and old (23 year-old) male and female Rhesus monkeys. In the cerebellum, cPLA2 protein level was higher in the young brain as compared to levels seen at both middle-aged and old. Similarly, in the frontal pole, the young brain showed a higher level of COX-2 protein as compared to the levels seen at both older ages. For both, once an animal reached 8–11 years of age the levels appeared to remain relatively constant over the next decade. Immunohistochemistry of COX-2 protein within the brain demonstrated no significant change in the localization to neurons within the frontal pole. In the young brain, the distribution of a low level of COX-2 protein within numerous neurons was different than the decreased number of neurons stained at a greater intensity in the adult brain. Based on the previous reports of localization of cPLA2 and COX-2 at post-synaptic sites in neurons results from the current study suggest that the elevated protein levels of the two enzymes seen in the younger brain is related to the greater potential for synaptic plasticity across multiple neurons as a function of age and that cPLA2 and COX-2 may be considered as post-synaptic markers.