Aluminum alloy heat exchange tube is attractive for the Low Temperature-Multi Effect Distillation (LT-MED) desalination device, for its low cost and excellent mechanical property. The corrosion damage is the key issue that influences on its service life. In this work, the corrosion inhibition of the bio-based melatonin (MEL) on AA5052 aluminum alloy in 3 wt.% NaCl solution under negative pressure is investigated by the weight-loss method and the electrochemical measurements. The decrease of the operation pressure makes the corrosion potential of AA5052 aluminum alloy to move positively and decreases its corrosion rate significantly. The corrosion potential and the critical pitting potential shift to the positive direction in the presence of MEL under different pressure. The MEL inhibits the corrosion of AA5052 aluminum alloy in 3 wt.% NaCl solutions very well. The corrosion inhibition efficiency of MEL decreases evidently under negative pressure. The decrease of pressure can change the surface films of aluminum alloy and thus affects effectively the adsorption behavior of the MEL.