This study presents the investigation of pressure drop with mass flow rate in PDMS microchannels with varying elasticity. Four microchannels with constant diameter of 0.289 mm were fabricated with different ratios of PDMS to curing agent (i.e. 5:1, 10:1, 15:1 and 20:1) and deployed for this study. Pressure drop has been measured in each channel for the range of mass flow rates varying from 1 to 20 ml/min (Re = 80–1440) using peristaltic pump in order to introduce the pulsating flow. Experimental results reveal distinctly contrasting trends in both sets of channels, with the soft-walled channels notably exhibiting a decrease in pressure drop with increase in softness. This can be attributed to deformations in the walls, which when observed using an inverted microscope, reveal significant expansions in soft walled channels, illustrating increasing effects under different flow rates. Our results reveal the clear differences caused by different flexibilities of PDMS samples on pressure drop for Newtonian Fluids under pulsating flow condition.