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Aim: To study the effect of selective interleukin-1 β-converting enzyme (ICE,caspase-1) inhibitor on ischemic acute renal failure (ARF). Methods: Mouse models of ischemic ARF were treated with the specific ICE inhibitor AC-YVAD-CMK.A renal function assay and renal morphological studies were employed to estimate the renal protective effect of AC-YVAD-CMK. The survival rate of mouse models was also analyzed by a time series test. Furthermore, renal ICE activity,mature interleukin-18 (IL-18) protein expression and interferon-γ (IFN-γ) mRNA expression were also detected by fluorescent enzyme-linked immunosorbent assay (ELISA), ELISA, and semi-quantitative reverse transcription-polymerase chain reaction, respectively. Results: The levels of blood urea nitrogen (BUN) and serum creatinine (Scr) increased remarkably in the model controls compared with the sham-operated groups (P＜0.01). Typical renal tubular necrosis was found in the model controls. Renal ICE activity, mature IL-18 protein expression, and IFN-γmRNA expression were also increased significantly in the model controls compared with the sham-operated groups. The levels of BUN and Scr in the AC-YVAD-CMK therapy group were decreased significantly compared with the untreated model controls (P＜0.01). Renal tubulointerstitial lesion was also attenuated significantly (P＜0.05). AC-YVAD-CMK therapy alleviated the clinical features of ARF, and increased the survival rate (P＜0.01). Furthermore, AC-YVADCMK therapy also decreased ICE activity, mature IL-18 protein expression, and IFN-γ mRNA expression in renal tissue (P＜0.05). Conclusion: The selective ICEinhibitor AC-YVAD-CMK can effectively protect the kidney from acute ischemic lesions. This protective effect is associated with decreased renal ICE activity and suppressed IL- 18 maturation and IFN-γ mRNA transcription.