Experimental investigation and numerical simulation on the effect of surface wettability on the performance of a polydimethylsiloxane (PDMS) based diffuser micropump are presented. A valveless micro membrane pump with piezoelectric actuation has been examined. Using a replica molding technique, the valveless micropump was made of PDMS on a Pyrex glass substrate. A thin piezoelectric (PZT) disc was used as an actuator. Poly vinyl alcohol (PVA) and octadecyltrichlorosilane (OTS) coatings, which make the coated surface hydrophilic and hydrophobic, respectively, were used to modify the surface wettability inside the pump. In our experiments, the contact angle of the PDMS surface changed from 96.6 o to 29.1 o and 99.6 o by PVA and OTS coatings, respectively, and the contact angle of glass changed from 33.2 o to 17.5 o and 141.8 o. A self-priming process was numerically simulated in a diffuser element using a computational fluid dynamics program (CFD-ACE+). The results show that fewer gas bubbles were created in the hydrophilic coated pump than in the hydrophobic coated one as time progressed. This agrees well with experimental observations. Steady-state flow rates of the micropump were measured. Compared to the non-coated pump, the flow rate increased slightly with the hydrophobic coating but decreased with the hydrophilic coating. We determine that surface wettability significantly affects the performance of a PDMS-based micropump.