Objective To explore the relationship between acute rejection and expression levels of perforin mRNA in peripheral blood and bile after rat liver transplantation so as to look for a kind of noninvasive method to diagnose acute rejection. Methods Rat orthotopic liver transplantation model with biliary extra-drainage was established. They were divided into 4 groups: blank control group (n=20)， isograft group (n=30)， allograft plus cyclosporine A (CsA) group (n=30) and allograft group (n=30). Semi-quantatative RT-PCR was used to measure the expressions of perforin mRNA in bile and peripheral blood and the pathological changes of the graft were observed on postoperative days of 1, 3, 5, 7 and 10. Results Blank control group and isograft group showed no expression of perforin mRNA in peripheral blood. The expression of perforin mRNA of peripheral blood in allograft group could be detected on day 3 after transplantation and it gradually elevated on day 5 and remained in high level during 7-11 days. In allograft plus CsA group perforin mRNA of peripheral blood continuously expressed in a low level, and the level at the same time points was significantly different compared with allograft group (P＜0.05). The expression of perforin mRNA in peripheral blood was analogous with the severity degree of histologic damage. The expression of perforin mRNA can not be found in bile. Conclusion The expression of perforin mRNA in the peripheral blood offers a sensitive and noninvasive means of monitoring acute rejection.