We examined the physical chemistry underlying a wet chemical etching-assisted femtosecond laser microfabrication technique. Close scrutiny of etching reagents and the etching process has led to further refinement of the method for practical use such as microchips for chemical total analysis systems (μ-TAS). Microchannels as long as a centimeter scale with less than 60 μm diameter (aspect ratio of ∼200) were fabricated inside vitreous silica substrates. In this regard, we demonstrated that a concentrated aqueous solution of KOH is advantageous over commonly used aqueous HF because of least saturation behavior in elongating channel structures. Resultant nearly twice as large the etching selectivity of KOH as that of HF allowed substantial penetration depths within the laser-modified volume while leaving the unmodified regions practically intact. Furthermore, the mechanism of laser-modification that permits highly selective wet etching was investigated by photoluminescence and confocal Raman spectral measure...