Aeromonas veronii can enlist- a variety of diseases such as sepsis in humans and animals. However, there has been no effective way to eradicate A. veronii. In this study, the intracellular antibacterial activities of the C-terminal aminated marine peptide N6 (N6NH(2)) and its D-enantiomer (DN6NH(2)) against A. veronii were investigated in macrophages and in mice, respectively. The result showed that DN6NH(2) with the minimum inhibitory concentration (MIC) of 1.62 mu M is more resistant to cathepsin B than N6NH(2) (3.23 mu M). The penetration percentages of the cells treated with 4-200 mu g/mL fluorescein isothiocyanate (FITC)-DN6NH(2) were 52.599.6%, higher than those of FITC-N6NH(2) (27.0-99.1%). Both N6NH and DN6NH(2) entered macrophages by macropinocytosis and an energy-dependent manner. DN6NH(2) reduced intracellular A. veronii by 34.57%, superior to N6NH(2) (19.52%). After treatment with 100 mu g/mL DN6NH(2), the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1 beta were reduced by 53.45%, 58.54%, and 44.62%, respectively, lower than those ofN6NH(2) (15.65%,12.88%, and 14.10%, respectively); DN6NH(2) increased the IL-10 level (42.94%), higher than N6NH(2) (7.67%). In the mice peritonitis model, 5 mu mol/kg DN6NH(2) reduced intracellular A. veronii colonization by 73.22%, which was superior to N6NH(2) (32.45%) or ciprofloxacin (45.67%). This suggests that DN6NH(2) may be used as the candidate for treating intracellular multidrug-resistant (MDR) A. veronii.