Honeybee brain has distHoneybee brain has distinct anatomical and functional regions, knowledge on molecular underpinnings of sub-organ to achieve the distinct neural function and the difference between the eastern and western honeybees are still missing. Here, the proteomes of three sub-organs of eastern and western honeybee brains were compared. Mushroom bodies (MBs) and optical lobes (OLs) may by employed similar proteome architectures to drive their domain-specific neural activity in both bee species. In MBs, protein metabolism and Ca2+ transmembrane transport are the key role players in driving the learning and memory by modulating the synaptic structure and signal transduction to consolidate memory trace. In OLs, ribonucleoside metabolism and energy production play major roles to underpin visual system by maintaining G-protein cycle and membrane electrical charge potential. However, in antennal lobes (ALs), it has evolved distinct proteome settings to prime the olfactory learning and memory in two bee species. In ALs of Apis cerana cerana (Acc), actin cytoskeleton organization is key for plasticity of glomeruli and intracellular transport to sustain the olfactory signaling. Whereas, in ALs of Apis mellifera ligustica (Aml), hydrogen and hydrogen ion transport are vital to support olfactory process by supplying energy and maintaining molecule transport. Noticeably, in ALs of Acc, the exclusively enriched functional groups acting as second messenger and neurontransmitter of signal transduction, and the enhanced protein metabolism to regulate the plasticity of synaptic structure for formation of memory, suggest that Acc may have evolved a better sense of smell than that of Aml. Our first proteome data is helpful as starting point for further analysis of neural activity in brain sub-area of honeybee and other insects.inct anatomical and functional regions, knowledge on molecular underpinnings of sub-organ to achieve the distinct neural function and the difference between the eastern and western honeybees are still missing. Here, the proteomes of three sub-organs of eastern and western honeybee brains were compared. Mushroom bodies (MBs) and optical lobes (OLs) may by employed similar proteome architectures to drive their domain-specific neural activity in both bee species. In MBs, protein metabolism and Ca2+ transmembrane transport are the key role players in driving the learning and memory by modulating the synaptic structure and signal transduction to consolidate memory trace. In OLs, ribonucleoside metabolism and energy production play major roles to underpin visual system by maintaining G-protein cycle and membrane electrical charge potential. However, in antennal lobes (ALs), it has evolved distinct proteome settings to prime the olfactory learning and memory in two bee species. In ALs of Apis cerana cerana (Acc), actin cytoskeleton organization is key for plasticity of glomeruli and intracellular transport to sustain the olfactory signaling. Whereas, in ALs of Apis mellifera ligustica (Aml), hydrogen and hydrogen ion transport are vital to support olfactory process by supplying energy and maintaining molecule transport. Noticeably, in ALs of Acc, the exclusively enriched functional groups acting as second messenger and neurontransmitter of signal transduction, and the enhanced protein metabolism to regulate the plasticity of synaptic structure for formation of memory, suggest that Acc may have evolved a better sense of smell than that of Aml. Our first proteome data is helpful as starting point for further analysis of neural activity in brain sub-area of honeybee and other insects.