Infancy marks a critical phase in brain development, laying the foundation for long-term neurological well-being. Pediatric traumatic brain injury (pTBI) and its associated neuroinflammatory response pose significant challenges, impeding proper brain development and exacerbating adverse outcomes. Here, we introduce a novel pTBI model in C57BL/6 mice and explore the effects of neonatal oxytocin (OT) treatment on microglial reactivity through chemogenetic manipulation. Our morphological and transcriptomic analyses unveil a notable increase in microglial reactivity at both cellular and molecular levels in animals subjected to pTBI, characterized by enhanced proliferation and a pro-inflammatory phenotype 24 hours post-insult. Remarkably, OT treatment effectively reverses these pro-inflammatory changes in microglia and mitigates TBI-induced gene expression pathways promoting inflammation. These findings underscore the therapeutic potential of OT as an intervention for pTBI, offering new avenues for managing neuroinflammatory responses in early brain injury.