Objective To explore the effect of pharmacological preconditioning wtith low-dose FK506 reducing subsequent ischemia-reperfusion injury in rabbit knee joint and to explore the possible mechanism of that. Methods Twenty four animal model of allograft heterootopic knee joint were established and divided randonly into three groups: IR group ( Ischemia-reperfusion group), KK506 group ( FK506 preconditioning group) and ST group(Sham control group). Vessels were clamped for 1 hour, and then grafts received reper-fusion. Tissues(for example muscles tissues) of pro-ischemia and reperfusion after 12 hours were obtained, and they were observed by microscope and electron microscope and were at aiysised with reverse transcription-polymerase chain reaction( RT-PCR) , Western Blot, DNA ladder, flow cvtometer. Moreover, the contents of MDA , NO and SOD in these tissues were examined by spectrophotometer Results As a result, we observed disoranized tissues and swollen cells in IR groups but trenchant tissues and intact cells in FK506 groups by microscope, vaeuolated and tumid mitochondrion in IR groups but non-vacuolated and intact that in FK506 groups. With FK506 preconidtioning, the contents MDA and NO were distiactly reduced but significant raised in FK506 group. Compared with IR group, DNA ladder of FK506 group were weakly, and apoptotic raetes reduce from 20% to 10% and the expression of TNF, IL-1 , Fas and FasL mRNA obviously down-regulated. At the same time, expression of HSP70 significantly up-regulated on protein and mRNA levels with RT-PCR and Western blotting analysis in FK506 group. Conclusion Pharmacological preconditioning with low-dose FK506(0. 3mg/kg) can induce tolerance of ischemia-reperfusion injury in rabbit allograft knee joint. Over-expression of HSP70 may he key factor of that.