Abstract: In recent years, the femtosecond laser becomes a promising tool to fabricate 3D microstructures for their applications in micro-optics, microfluidics and biofabrication. Various femtosecond-laser-based processes have been used for machining high-precise microstructures with arbitrary shapes. However, the efficiency problem of the femtosecond laser micro-fabrication has hindered its practical applications. Here we present a simple, high-efficient maskless technique to fabricate 3D microstructures on glasses using a femtosecond laser wet etch (FLWE) process. In the FLWE process, the ultrafast laser delivers intensity and time-controlled, programmable arranged, individual pulses to a glass chip. The sample is then subjected to wet-etch processing. The laser pulses change the physical and chemical properties of the glass in the focal spots, and the wet-etch processing that follows carves out a unique 3D microstructures array pattern. Using this method, we fabricated microlens with the diameter: 80 m, height: 6.7 m and surface roughness: less than 10 nm. We fabricated microstructures on glass surface like microlens arrays with different characteristics like high-fill ratio, high-aspect ratio, controllable shape and arrange, and so on. We also fabricated microstructures like spiral microchannels inside glasses using the FLWE process. The diameter of the spiral microchannel is 20 m, and the length-diameter ratio is more than 100. These 3D microchannels will be served as the alternatives of the 2D microstructures in the conventional microfluidic devices.