Pressure drop in a gas-liquid slug flow through a long microchannel of rectangular cross-section was investigated. Pressure measurements in a lengthy (∼0.8 m) microchannel determined the pressure gradient to be constant in a flow where gas bubbles progressively expanded and the flow velocity increased due to a significant pressure drop. Most of the earlier studies of slug flow in microchannels considered systems where the expansion of the gas bubbles was negligible in the channel. In contrast, we investigated systems where the volume of the gas phase increased significantly due to a large pressure drop (up to 1811 kPa) along the channel. This expansion of the gas phase led to a significant increase in the void fraction, causing considerable flow acceleration. The pressure drop in the microchannel was studied for three gas-liquid systems; water-nitrogen, dodecane-nitrogen, and pentadecane-nitrogen. Inside the microchannel, local pressure was measured using a series of embedded membranes acting as pressure sensors. Our investigation of the pressure drop showed a linear trend over a wide range of void fractions and flow conditions in the two-phase flow. The lengths and the velocities of the liquid slugs and the gas bubbles were also studied along the microchannel by employing a video imaging technique. Furthermore, a model describing the gas-liquid slug flow in a long microchannel was developed to calculate the pressure drop under conditions similar to the experiments. An excellent agreement between the developed model and the experimental data was obtained.