Membrane fouling still posts as one of the major obstacles in membrane distillation (MD). This is why the MD approach still cannot successfully compete with other conventional seawater desalination methods. In this study, both the NaCl solution and real seawater are used as the feed of MD processes to investigate the differences in permeate flux, product water quality and membrane fouling. The results indicate the accumulation rate of membrane scale can be depressed by reducing the degree of polarization if NaCl solution is used as the feeding fluid, however, this kind of depression effect is not so obvious when real seawater is used as the feeding fluid. An ultrasonic cleaning technique is found to be an effective way to restore the flux rate for these MD processes and extend the life span of MD membrane.