Numerical simulation of heat transfer of nanofluids in rectangular microchannel has been performed. A micro-electro-mechanical system is built with two heating resistors embedded in a silicon substrate. Microchannel made from polydimethylsiloxane is planted in the substrate and nanofluids with different volume fractions are used as the coolant. Because of the not well-insulated micro-electro-mechanical system, heat generated by the heating resistors will be lost to the surrounding as well as carried away by the nanofluids through the microchannel. Heat transfer is analyzed at low Reynolds number for different nanofluid concentrations.