In the experiments conducted at Purdue, the air flow in rectangular cross-section microchannels was investigated using pressure sensitive paint. The high resolution pressure measurements were obtained for inlet-to-outlet pressure ratios from 1.76 to 20 with the outlet Knudsen numbers in the range from 0.003 to 0.4 based on the hydraulic diameter of 151.7 µm and the length-to-height ratio of about 50. In the slip flow regime, the air flow was simulated by the 2D and 3D Navier–Stokes equations with no-slip and slip boundary conditions. For various pressure ratios, the entrance flow development, compressibility and rarefaction effects were observed in both experiments and numerical simulations. It was found that the accurate modeling of gas flows in finite-length channels requires the inlet and outlet reservoirs to be included in computations. Effects of entrance geometry on the friction factor were studied for 3D cases. In both experiments and numerical modeling, significant pressure drop was found starting at the inlet chamber. The numerical modeling also predicted an apparent temperature drop at the channel exit.