Serotonergic signaling has shown to be a key player in the modulation of social behavior. Specifically, serotonin type 2A receptors (5-HT2AR), known to be involved in a variety of behaviors, have also been linked to social cognition through the pathophysiology of different psychiatric and neurodevelopmental disorders, and its role in the mechanism of action of so-called “prosocial” drugs. Our lab found that 5-HT2AR knockout (htr2a-/-) had reduced discrimination indexes in the three-chambers social interaction test (SIT) compared to wild types (htr2a+/+) mice. By genetically restoring the expression of 5-HT2AR in the forebrain, mice reached discrimination indexes similar to htr2a+/+. Moreover, acute blockade of 5-HT2AR with MDL 11939 in htr2a+/+ mice before the SIT did not affected discrimination indexes, suggesting that the receptor is not acutely recruited in this task. Finally, preliminary results of c-fos expression analysis post SIT showed differential expression between htr2a+/+ and htr2a-/- mice. In conclusion, these findings suggest that 5-HT2AR plays a role in social behavior, with a possible sex-specific modulation, and highlight the distinct roles of this receptor in social cognition under acute versus developmental manipulations.