Social insects form complex societies with division of labor between different female castes. In most species, a single queen heads the colony; in others, several queens share the task of reproduction. These different social organizations are often associated with distinct queen morphologies and life history strategies and occur in different environments. In the ant Temnothorax rugatulus, two queen morphs - macrogynes and microgynes - exist associated with mono- and polygynous colonies, respectively, which occur at lower and higher elevations. We analyzed plastic changes in brain transcriptomes in response to the social environment in these queen morphs and their workers. We manipulated the number of queens over several weeks to investigate whether transcriptional activity is influenced by queen morph, social environment, or their interaction. Changes in gene expression in the queens’ brains in response to our manipulations were subtle and largely influenced by the interaction between social environment and queen morph, rather than independently by these factors. Macrogynes and microgynes thus adjust differently to their social environment. Similarly, worker transcriptomes were influenced by an interaction between behavioral type, i.e., nurses or foragers, and queen morph. Nurses differentially regulated genes related to nutrition depending on queen morph, suggesting a link between social environment and metabolic dynamics in ant colonies. Overall, our study shed light on how the social environment influences the molecular physiology of social insects. Furthermore, we demonstrate that in this ant with two queen morphs, worker physiology depends on queen morph and their role in the colony.