The effect of microcosmic morphologies of textured Cu surface by nanosecond laser on the inert wetting and reactive wetting, i.e., ethylene glycol/copper and tin/copper wetting systems, was studied by using modified sessile drop methods. To create different surface roughness, the microcosmic morphologies with different spacing of grooves were constructed by nanosecond laser. The results showed that the inert wetting (ethylene glycol/copper) was consistent with Wenzel model, while the reactive wetting results deviated from the model. In Sn/Cu reactive wetting system, the interfacial evolution in the early stage and the pinning of triple line by the precipitated h-Cu6Sn5 caused the rougher surface and the worse final wettability. When the scale of artificial roughness exceeded the roughness that was caused by interfacial reaction after reaching the quasi-equilibrium state at interface, the final wettability could be improved.