In conventional injection molding, the molten polymer in the filling stage is generally assumed to be incompressible. However, this assumption may not be valid in micro-injection molding, since high injection pressure is normally required to avoid short shots. This paper presents both numerical and experimental investigations on the effects of polymer melt compressibility on mold filling into a micro-thickness impression. The study was conducted on six different part thicknesses ranging from 920 to 370 µm. A high-flow COC TOPAS 5013L-10 polymer was chosen as the TOPAS family has recently attracted significant interest for its use in microfluidic applications. A combined finite element/finite difference/control volume approach was adopted to simulate the compressible flow. The shear viscosity of a polymer melt was characterized by the Cross-WLF model, while the melt compressibility was modeled with a double-domain Tait equation. The results obtained indicated that the compressibility of the polymer melt has significant effects on impression pressure and density distribution in the fully filled part with thickness smaller than 620 µm and that the effects become more pronounced with a decrease in part thickness.