The fluid flow and heat transfer characteristics in a three dimensional (3D) rectangular shaped microchannel heat sink (MCHS) with Al2O3-water nanofluids is numerically investigated. The thermal and flow fields are analyzed using different Reynolds numbers and nanoparticles with different concentrations. The 3D, steady, laminar flow and heat transfer governing equations are solved by finite volume method using ANSYS 14.0. The evaluating parameter such as temperature, heat transfer coefficient and pressure drop are obtained from the simulation. Results show enhanced performance with the usage of nanofluids, and slightly penalty in pressure drop. The increase in Reynolds number leads to increase in heat transfer rate as well as pressure drop and power.