Objective To investigate the relationship between NF-κB activity and IFN-γ gene expression, as well as the histopathological changes following liver transplants, both with and without cyclosporin A (CsA) treatment. Methods Sixty male Wistar and Thirty male SD rats were subjected to orthotopic liver transplants. Fourty-five of the Wistar rats were used as recipients, and were divided into 3 groups: group Ⅰ, syngeneic control (Wistar-to-Wistar); group Ⅱ, acute rejection (SD-to-Wistar ); and group Ⅲ: acute rejection treated with cyclosporin A by intramuscular injection (SD-to-Wistar+CSA). After the liver transplants, electrophoretic gel mobility shift assay was used to analyze NF-κB activity in the splenocytes of recipient rats, and RT-PCR was used to measure IFN-γ gene expression in grafted liver specimens. In addition, histopathological examinations were performed to assess the severity of acute liver rejection. Results In group Ⅰ, low levels of NF-κB activity were only detectable on day 5 and 7 post-transplant, and only weak IFN-γ mRNA expression was observed at all time points. By contrast, both high NF-κB activity and high expression levels of IFN-γ mRNA were detected at all time points in group Ⅱ. In group Ⅲ, NF-κB activity and IFN-γ mRNA expression were significantly inhibited, as compared to group Ⅱ (P<0.05). A good correlation was found between NF-κB activity and IFN-γ mRNA expression (r=0.815). In addition, NF-κB activity and IFN-γ mRNA expression mirrored histopathological changes in all three experimental groups.Conclusions Changes in IFN-γ mRNA expression levels after liver transplantation are at least partially due to changes in levels of NF-κB activity. CsA appears to downregulate NF-κB activity, thus inhibiting IFN-γ gene transcription. Blocking the NF-κB mediated transcription pathway may be of benefit in preventing liver transplant rejection.