Objective To investigate the effect and mechanism of dexmedetomidine, mifepristone and dexmedetomidine plus mifepristone on the fear memory in rats with post?traumatic stress disorder ( PTSD) . Methods 40 male SD rats were randomly divided into five groups with 8 in each group:control group (group C),PTSD model group (group P),dexmedetomidine group (group D),mifepristone group ( group M) and dexmedetomidine plus mifepristone group ( group U) . Fear memory in rats was evaluated by fear conditioning test ( FC) . Anxiety?like behavior was assessed by the elevated plus?maze test ( EPM) . Ex?pressions of BDNF and its receptor TrkB in the hippocampus of rats after fear condition were detected using Western blot ( WB) and CORT level in the serum was detected using enzyme?linked immunosorbent assay (ELISA). Results Compared with group P,the freezing scores in the FC in group D((32.29±8.09) %), M((33.33±8.21) %),and U((9.38±3.31) %) were significantly decreased (P<0.05). The times and en?tries in the open arms of the EPM were significantly increased (P<0.05) . The expressions of BDNF in group D(0.65±0.04),M(0.71±0.04),U(0.79±0.07) and TrkB in group D(0.66±0.04),M(0.71±0.04),U (0.86±0.03) were obviously rescued in hippocampus of rats (P<0.05). The CORT level in serum in group D ((37.65±12.37)μg/L) and U((59.10±5.23)μg/L) was decreased (P<0.05). There was no difference be?tween group P and M. Conclusion These results suggest that dexmedetomidine, mifepristone and dexme?detomidine plus mifepristone can significantly enhance fear extinction and improve anxiety?like behaviors in rats with PTSD. The mechanism may be that dexmedetomidine and mifepristone could enhance the expres? sions of BDNF and TrkB in the hippocampus.