Abstract： Objective To investigate the potential preventive role of small interfering RNA targeting ICAM-1 (ICAM-1siRNA) infusion through renal artery in renal transplant cold ischemia injury model. Methods Fisher rats underwent renal isografting. Following removal, the left kidney was preserved in 0 to 4℃ heparin normal saline (NS) solution for 1 h to reinforce the cold ischemia injury. Before transplant, either ICAM-1siRNA (0.1 mg/kg), or (NS) or control siRNA was infused through the renal artery with the renal vein clamped ex vivo. The left kidney was then implanted and the right kidney was removed. At 6, 12, 24, 48 and 72 h post-operation, serum Cr was measured, and the severity of tubular necrosis and inflamed cells infiltration was assessed by histological grading scale respectively. The expression of ICAM-1 mRNA and protein in isograft was detected by real-time RT-PCR and Western blot, respectively. Results Compared with the NS and control siRNA groups, the values of serum Cr in siRNA group were lower at every time point, and the difference after 12 h was statistically significant (P = 0.01～0.001), but there was no significant difference between NS and control siRNA groups (P>0.05). The tubular necrosis and inflamed cells infiltration were less severe in siRNA group than those in NS and control siRNA groups, with the difference being significant especially in 12, 24 and 48 h. After 12 h, the expression levels of ICAM-1 mRNA and protein in the kidney of siRNA group were significantly down-regulated as compared with NS and control siRNA groups, and the difference reached its peak at 24 h. There was no significant difference among 3 groups at 72 h (P>0.05). Conclusion ICAM-1siRNA can significantly prevent and attenuate the renal damage secondary to ischemia by down-regulating the expression of ICAM-1 protein and mRNA.