Calcium/calmodulin-dependent protein kinase II (CaMKII) has been linked to neuronal plasticity associated with long-term potentiation as well as structural synaptic plasticity. Previous work in adult honeybees has shown that a single CaMKII gene is strongly expressed in the mushroom bodies (MBs), brain centers associated with sensory integration, and learning and memory formation. To study a potential role of CaMKII in synaptic plasticity, the cellular and subcellular distribution of activated (phosphorylated) pCaMKII protein was investigated at various life stages of the honeybee using immunocytochemistry, confocal microscopy, and western blot analyses. Whereas at pupal stages 3–4 most parts of the brain showed high levels of pCaMKII immunoreactivity, the protein was predominantly concentrated in the MBs in the adult brain. The results show that pCaMKII is present in a specific subpopulation of Kenyon cells, the noncompact cells. Within the olfactory (lip) and visual (collar) subregion of the MB calyx neuropil pCaMKII was colocalized with f-actin in postsynaptic compartments of microglomeruli, indicating that it is enriched in Kenyon cell dendritic spines. This suggests a potential role of CaMKII in Kenyon cell dendritic plasticity. Interestingly, pCaMKII protein was absent in two other types of Kenyon cells, the inner compact cells associated with the multimodal basal ring and the outer compact cells. During adult behavioral maturation from nurse bees to foragers, pCaMKII distribution remained essentially similar at the qualitative level, suggesting a potential role in dendritic plasticity of Kenyon cells throughout the entire life span of a worker bee. J. Comp. Neurol. 519:3700-3712, 2011. © 2011 Wiley-Liss, Inc.