Abstract: Aiming at the poor quality and low efficiency of PMMA microfluidic channel machining, the fabrication process technology of PPMA microfluidic channel with direct-writing femtosecond laser was studied. The effects of different laser parameters on the width, depth, roughness of the microfluidic channel, and the crater height of the deposits on both sides of the micro-channel were analyzed, as well as the changing rules.The experimental results show that when the laser scanning speed is 20 mm/s and the laser power is 0.5 W, the roughness of the microfluidic channel is low and the variation range is not obvious; when the laser energy increases from 0.5 W to 0.75 W, the width and depth of the microfluidic channel increase linearly with laser energy; when the laser power is greater than 0.5 W, the width, depth, roughness of the microfluidic, and the height of the crater of the deposits gradually increase with the increase of the laser power and the number of processing times. After calculation, the ablation threshold of PMMA is 0.357 J/cm². By optimizing the process parameters, the microfluidic channel chip with low roughness, smooth surface and depth of 16 μm was prepared.