Flow instabilities, such as flow excursion, flow maldistribution, and pressure-drop oscillation, are caused by the negative resistance of the pressure drop vs. flow rate characteristics in two-phase flow system, being rather classical issues in two-phase flow dynamics. Previous investigations were mainly based on lumped-parameter modellings, and thus distributed-parameter analyses were rather few because the occurrences of flow instabilities depend simply on whether the system has negative-resistance characteristics. The negative-resistance instabilities are not limited in such boiling systems, and are often encountered in isothermal gas–liquid two-phase flow through mini channels. The present article describes such flow instabilities in an isothermal system. In mini- and micro-channels, surface tension dominates the flow pattern formation, and the pressure drop characteristics are affected accordingly so that the negative-resistance characteristics appear. The present investigation focuses on the extension of the “discrete bubble model” developed by the authors. The present extended version of the model is applied to simulate the negative-resistance characteristics of the pressure drop, the pressure-drop oscillation, and the drastic flow maldistribution in an isothermal two-phase flow system. The static and dynamic behavior of two-phase flow in mini-channels is well reproduced by the present numerical simulation, and the applicability of the model is verified through the comparison with existing experimental results. © 2019 by Begell House, Inc. www.begellhouse.com