The aim was to analyze the effects of low dose rate neutron-gamma mixed irradiation on the mRNA expression of hepatic cholesterol 7α-hydroxylase (CYP7A1) gene in the rat and its potential mechanism. Sixty rats were randomly divided into 4 groups: irradiated group in which 20 rats were irradiated for 14 d; control group in which 10 rats were sham irradiated for 14 d; irradiated group in which 20 rats were irradiated for 31 d; control group in which 10 rats were sham irradiated for 31 d. The irradiated rats were irradiated with low dose rate 60Co γ-rays at 0.0167 Gy•h−1 for 2 h and 252Cf neutron at 0.028 mGy•h−1 for 20 h. After being irradiated for 14 d and 31 d, 20 irradiated rats and 10 control rats were killed respectively. The total RNA was extracted from livers. The real-time PCR was used to detect the expression level of hepatic CYP7A1 gene and some nuclear receptor genes, such as peroxisome proliferator activated receptor alpha (PPARα), farnesoid X receptor (FXR), pregnane X receptor (PXR), hepatocyte nuclear factor 4 alphas (HNF4?) and liver X receptor alpha (LXR?), which involved in CYP7A1 transcriptional regulation. The results showed that the mRNA level of hepatic CYP7A1 gene in the irradiated rats which were irradiated for 14 d significantly decreased by 44%( p<0.01) of that in the control group rats, the mRNA level of hepatic PXR gene in the irradiated rats which were irradiated for 14 d increased by 1.69-fold of that in the control group rats, while the mRNA levels of PPARα, FXR, HNF4α and LXRα in the irradiated rats which were irradiated for 14 d did not change significantly compared with the control rats; the mRNA level of hepatic CYP7A1 gene in the irradiated rats which were irradiated for 31 d rather significantly decreased by 22%(p<0.01) of that in the control rats, the mRNA level of hepatic PXR gene in the irradiated rats which were irradiated for 31 d significantly increased by 2.34-fold (p<0.01) of that in the control rats, while the mRNA levels of PPARα, FXR, HNF4α and LXRα in the irradiated rats which were irradiated for 31 d didn’t change significantly compared with the control rats. Thus, after exposure to low dose rate neutron-γ rays co-irradiation in a period, the mRNA level of hepatic CYP7A1 gene in the rat significantly decreased with the accumulation of the absorbed dose. The possible mechanism of the change was that the co-irradiation led to the significant increase transcriptional level of PXR gene, but PXR repressed the transcription of CYP7A1 gene.Cited