This paper attempts to explore the variable mass flow in horizontal well from both experimental and numerical perspectives. For this purpose, a simulation model was created for single-phase liquid and gas-liquid two-phase variable mass flows in the wellbore using the FLUENT simulation software, and applied to the computational fluid dynamics (CFD) simulation of the variable mass flows in a horizontal pipe. Then, several experiments were carried out on the single phase variable mass flow in three scenarios, the unperforated horizontal pipe, the horizontal pipe with one perforation, and the horizontal pipe with two perforations. Through the analysis, the author established linear regression equations regarding the relationship of mixture pressure drops caused by the perforation-main pipe flow ratio. The main conclusions of the research are as follows: First, in both single-phase and gas-liquid two phase flows, the pressure drop across the perforation process increases with the perforationmain pipe flow ratio, under the same total flow rate. The trend is independent of the number of perforations. The simulation results agree well with the experimental data. Second, for both single-phase and gas-liquid two-phase variable mass flows, the pressure drop across the perforation process increases with the main pipe velocities, when the perforation velocities remain the same. Third, the pressure drop of the horizontal pipe with one perforation is greater than the total pressure drop of the horizontal pipe with two perforations, as long as the total single-phase fluid flow rate and the main pipe flow remain the same. The trend is exactly the opposite when the total two-phase fluid flow rate and the main pipe flow remain unchanged. Fourth, for single-phase liquid flow, the friction factor of unperforated pipe obtained by the Colebrook equation is much smaller than that calculated from the experimental data. Based on the measured data, a new friction factor of the perforated horizontal pipe was presented through data fitting. Fifth, when the total flow rate remains the same for the single-phase liquid flow, the friction factor is much higher for perforated horizontal pipe than the unperforated horizontal pipe, but the proportion of the increment is relatively small. The research findings shed valuable new light on the variable mass flow in horizontal wellbore.