Cecropin A is a novel 37‐residue cecropin‐like antimicrobial peptide isolated from the cecropia moth, Hyalophora cecropia. We have demonstrated that cecropin A is an antibacterial agent and have investigated its mode of action. In this study, we show that cecropin A has potent antimicrobial activity against 2 multidrug resistant organisms—Acinetobacter baumanii and—Pseudomonas aeruginosa. Interactions between cecropin A and membrane phospholipids were studied using tryptophan blue shift experiments. Cecropin A has a strong interaction with bacterial cell mimetic membranes. These results imply that cecropin A has selectivity for bacterial cells. To address the potential the rapeutic efficacy of cecropin A, its anti‐inflammatory activities and mode of action in mouse macrophage‐derived RAW264.7 cells stimulated with lipopolysaccharide (LPS) were examined. Cecropin A suppressed nitrite production, mTNF‐α, mIL‐1β, mMIP‐1, and mMIP‐2 cytokine release in LPS‐stimulated RAW264.7 cells. Furthermore, cecropin A inhibited intracellular cell signaling via the ERK, JNK, and p38 MAPK pathway, leading to the prevention of COX‐2 expression in LPS‐stimulated RAW264.7 cells. These results strongly suggest that cecropin A should be investigated as a potential agent for the prevention and treatment of inflammatory diseases.