The medial prefrontal cortex has been associated with fear, anxiety and stress regulation, and has recently been suggested to play a crucial role in the development of behavioural changes in response to stress. In this study, we evaluated medial prefrontal cortex (mPFC) involvement in both anxiety-like behaviour and increased anxiety-like responses induced by uncontrollable restraint. Rats with mPFC electrolytic lesions (n=7) and sham-lesioned (n=8) were tested in the elevated T-maze (ETM). Restrained rats with mPFC lesions (n=8) and sham-lesioned rats (n=6) were tested in the elevated T-maze 24h after restraint. Both two-trial passive avoidance and one-trial escape behaviours were assessed. The results revealed that mPFC lesions impair passive avoidance, but not escape behaviour. In addition, decreased anxiety-like behaviour in both passive avoidance and escape behaviours were observed in restrained rats with mPFC lesions. Our results suggest that mPFC is important in mediating both anxiety-like behaviour expression and long-term anxiogenic-like effects induced by acute restraint.