Honeybees have evolved an intricate system of chemical communication to regulate their complex social interactions. Specific proteins involved in odorant detection most likely supported this chemical communication. Odorant reception takes place mainly in the antennae within hairlike structures called olfactory sensilla. Antennal proteomes of sexually mature drone and forager worker bees (an age group of bees assigned to perform field tasks) were compared using two-dimensional electrophoresis, mass spectrometry, quantitative real-time polymerase chain reaction, and bioinformatics. Sixty-one differentially expressed proteins were identified in which 67% were highly upregulated in the drones' antennae whereas only 33% upregulated in the worker bees' antennae. The antennae of the worker bees strongly expressed carbohydrate and energy metabolism and molecular transporters signifying a strong demand for metabolic energy and odorant binding proteins for their foraging activities and other olfactory responses, while proteins related to fatty acid metabolism, antioxidation, and protein folding were strongly upregulated in the drones' antennae as an indication of the importance for the detection and degradation of sex pheromones during queen identification for mating. On the basis of both groups of altered antenna proteins, carbohydrate metabolism and energy production and molecular transporters comprised more than 80% of the functional enrichment analysis and 45% of the constructed biological interaction networks (BIN), respectively. This suggests these two protein families play crucial roles in the antennal olfactory function of sexually mature drone and forager worker bees. Several key node proteins in the BIN were validated at the transcript level. This first global proteomic comparative analysis of antennae reveals sex-biased protein expression in both bees, indicating that odorant response mechanisms are sex-specific because of natural selection for different olfactory functions. To the best of our knowledge, this result further provides extensive insight into the expression of the proteins in the antennae of drone and worker honeybees and adds vital information to the previous findings. It also provides a new angle for future detailed functional analysis of the antennae of the honeybee castes.