A method of water-assisted laser induced plasma backside etching of Pyrex7740 glass is proposed and a scaled-down cross-channel microfluidic chip is fabricated. The influences of laser energy density and laser processing times on the average etching depth, and the function of deionized water in the etching process are studied by means of theoretical analyses and processing experiments. The study results show that the average etching depth depends much on the laser energy density and the processing times. The deionized water is helpful for the realization of a continuous etching, and a chip with microgroove width of 77.8 μm, etching depth of 20.4 μm, a neat etching edge of no obvious damages is fabricated. However, in the absence of deionized water, the maximum etching depth is 2.8 μm under a laser energy density of 3.4 J/cm2.