To develop a novel cell-selective antimicrobial peptide with potent anti-inflammatory activity as well as high bacterial cell selectivity, we synthesized a Leu/Lys-rich model peptide, KLW-f (KWKKLLKKfLKLfKKLLK-NH(2)) containing two Phe-peptoid residues in its middle position. KLW-f exhibited high antimicrobial activity (the MIC range: 0.5 approximately 2.0microM) against the tested six bacterial cells. In contrast, KLW-f was no cytotoxic to human red blood cells and HeLa and NIH-3T3 cells. KLW-f caused no or little dye leakage from EYPE/EYPG (7:3, w/w) vesicles (bacterial membrane-mimicking environments), indicating its bacterial-killing action is probably not due to permeabilization/disruption of bacterial cytoplasmic membranes. Furthermore, KLW-f induced a significant inhibition in LPS-stimulated NO production from mouse macrophage RAW264.7 cells at 10microg/ml. Taken together, our results suggest that KLW-f appear to have promising therapeutic potential for future development as a novel antisepsis agent as well as antimicrobial agent.