OBJECTIVE: Stress and fear conditioning are both involved in the development of affective disorders, but their interconnected relationship remains unclear. Here in this study we employed acute and chronic stress model to investigate their respective effect on fear conditioning and the CRFR1 signaling change in the limbic areas including mPFC, hippocampus and BLA. METHODS: Male rats were subjected to acute restraint stress or chronic unpredictable mild stress before open field test and fear condition test. In situ hybridization was used to investigate CRFR1 mRNA expression in limbic region including mPFC, hippocampus and BLA. RESULTS: Our results demonstrated that acute and chronic stress have opposite effects on the acquisition of fear conditioning, which is correlated to CRFR1 mRNA expression in hippocampus; however, they have similar effects on fear extinction and both facilitated contextual-related fear conditioning. CONCLUSION: Our findings revealed acute and chronic stress led to distinct behavioral responses in fear conditioning and indicated CRFR1 is involved in the interaction of stress and fear conditioning, which help understand the connection between stress and fear memory.