The pressure drop and friction factor for the flow in horizontal smooth microtubes were investigated experimentally over a wide variety of Reynolds numbers in the laminar region under hydrodynamically fully developed conditions. The plain pipes are fabricated from 316 stainless steel and provided by (Swagelok Co., USA) with inner diameters of 0.770 mm and 0.510 mm and the length is 500 mm for both microchannels. For this purpose, graphene oxide (GO) nanosheets and magnesium oxide (MgO) nanoparticles were synthesized then characterized using standard methods such as X-ray powder diffractometer (XRD) and Transmission Electron Microscope (TEM). The prepared GO and MgO nanomaterial were added to distilled water to prepare nanofluids with mass fractions of 0.25, 0.5, 0.75, and 1 wt.% as working fluids and passes through one end of the microchannel to the other by a magnetically coupled gear programmable pump with variable speed that drives it. This study predicts the behavior of fluid flow in the microchannel for the range of dimensions used. Comparisons of pressure drop characteristics are given in terms of nanoparticle mass fractions and tube diameters. As a result, MgO nanofluids recorded higher pressure drop with an increase in the concentration of the nanofluids due to its higher viscosity followed by GO nanofluids.