Exposure to psychosocial stress (e.g., bullying) in juveniles is a risk factor of stress-related psychiatric disorders later in life. The exposure to stress activates microglia, which plays an important role in brain immunity, and induces neuroinflammation. It is unclear to what degree the exposure to psychosocial stress as juveniles is affected to brain immunity systems and neuronal morphology. The present study was examined expression of inflammatory cytokines or inflammatory signal-related molecules and neuronal morphology in the prefrontal cortex (PFC) by using the mice exposed to social defeat stress as juveniles. We found that inflammation or immune system-related genes of defeated mice were significantly changed, compared to those of non-defeated mice in transcriptome analysis. Especially, the high expressions of Ca2+ binding protein, S100A8, and S100A9 genes were observed in the PFC of defeated mice. The levels of TNF-α and the numbers of spines in defeated mice were significantly increased and decreased, respectively, compared to that in non-defeated mice. There were no significant changes of TNFR1, NF-κB, or I-κB levels in defeated mice. Administration of R-7050, a TNF-α receptor antagonist, didn’t develop the impairment of social behaviors induced by social defeat stress exposure as juveniles. Our findings suggest that exposure to social defeat stress as juveniles induces TNF-α mediated neuroinflammation via the activated microglia.