Abstarct: The importance and developments of microfluidic devices, like expansion microchannel, has caused that the investigation of the flow and the heat transfer of nanofluid in sudden expansion microchannel to be so important. On the other hand, the two phase models can be used instead of single phase model very well. Among two phase models, Eulerian-Eulerian model is very efficient because of considering the relative velocity and temperature of the phases and the nanoparticle concentration distribution. In this study, laminar forced convection of CuO nanofluid is numerically investigated in sudden expansion microchannel with isotherm walls and different expansion ratios. An Eulerian two-fluid model is considered to simulate the nanofluid flow inside the microchannel and the governing mass, momentum and energy equations for both phases are solved using the finite volume method. In solving the flow equations for both phases, the SIMPLE algorithm is modified for the coupling of the velocity and pressure and the continuity equations for both phases are combined in order to create the pressure correction equations. However, the Eulerian – Eulerian modeling results show higher heat transfer enhancement in comparison to pure water, so that for a 2% copper-water nanofluid, it has been observed a 35% increase of the heat transfer. The heat transfer enhancement increases with increase in Reynolds number and nanoparticle volume concentration, while the pressure drop increases only slightly. Also, the heat transfer increases with decrease in the nanoparticle diameter so that a 2% copper-water nanofluid, for 50 nm particle size, the enhancement in heat transfer is 5% more in comparison to 100 nm particle size. Investigation of the expansion ratio of microchannel shows that the average Nusselt number increases with decrease in expansion ratio as well as with increase in Reynolds number.