Objective To investigate the effect of medial preoptic area ( mPOA) destruction on the anesthesia induced with propofol and ketamine and the role of mPOA in the mechanism of anesthesia. Methods Twenty-four SD rats weighing 250-300 g were randomly divided into two groups: NS group ( n = 12) and NMDA destruction group ( n = 12) . The animals were anesthetized with intraperitoneal (ip) pentobarbital 40 mg?kg-1. A hole was drilled in the skull fixed by a stereotactic apparatus (Narishige). 0.5?l of normal saline (NS) or N-methyl-D-aspartate (NMDA) was injected into mPOA. The rats were observed for changes in behaviour and body weight. On the 7 th day after NS or NMDA injection each group was further divided into 2 subgroups receiving either propofol 100 mg?kg-1 or ketamine 100 mg?kg-1 ip. The latency of loss of righting reflex (RL)(time from end of ip injection to loss of righting reflex) and recovery time (RT) were recorded. Results There were no significant changes in behaviour and body weight after mPOA injection in NS group; while animals in NMDA-destruction group showed increased excitability , irritability and activity and decreased appetite and sleep and significant weight loss after mPOA injection. RL was significantly longer and RT was significantly shorter after propofol/ketamine ip injection in NMDA destruction group than those in NS group. Conclusion mPOA is probably involved in anesthesia induced with propofol and ketamine.