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Background/Aim: Fas ligand (FasL) and tumor necrosis factor (TNF)- are major pro-apoptotic molecules and also induce inflammation through cytokine and chemokine production. Al-though precise intracellular mechanisms of action have been reported for each molecule, the differential impact of these molecules on kidney injury in vivo still requires clarification. Meth-ods: We explored the differential impact of FasL and TNF- upon apoptosis and inflammation in ischemic acute kidney injury using neutralizing anti-FasL antibodies and TNF- receptor 1 (TNFR1)-deficient mice. Results: TNFR1 deficiency was associated with a lesser anti-inflamma-tory effect upon leukocyte infiltration and tubular necrosis than treatment with anti-FasL anti-body. Furthermore, the number of TUNEL-positive cells was significantly reduced in anti-FasL antibody-treated mice, whereas it was only partially diminished in TNFR1-deficient mice. In vitro studies confirmed these findings. FasL administration induced both apoptosis and cytokine/ chemokine production from cultured tubular epithelial cells. However, TNF- had a limited ef-fect upon tubular epithelial cells. Conclusion: In ischemic acute kidney injury, FasL has a great-er impact than TNF- on the apoptosis and inflammatory reaction through cytokine/chemo