The thermal loads are increasing in a wide variety of applications like microelectronics, transportation, lighting, utilization of solar energy for power generation, etc. Micro-electro-mechanical systems (MEMS) technology and nanotechnology are also rapidly emerging as a new revolution in miniaturization. Heat exchangers play a very important role in energy conversion, transmission, and utilization. Hence, the management of high thermal loads in these systems offers challenges and the thermal conductivity of heat transfer uid has become vital. This implies that a detailed study is required in microchannels. In the present study, the pressure drop and laminar convective heat transfer characteristics of three different nanofluids of Al2O3 and CuO in microchannel heat sink with rectangular duct of serpentine shape are experimentally investigated and compared with numerical values. The optimization of the microchannel for enhanced heat transfer is done with varying the hydraulic diameter of the serpentine shaped microchannel to get the maximum pressure drop across the channel for improved thermal conductivity.