Many different types of microelectrodes have been developed for use as a direct Brain-Machine Interface (BMI) to chronically recording single neuron action potentials from ensembles of neurons. Unfortunately, the recordings from these microelectrode devices are not consistent and often last for only a few weeks. For most microelectrode types, the loss of these recordings is not due to failure of the electrodes but most likely due to damage to surrounding tissue that results in the formation of nonconductive glial-scar. Since the extracellular matrix consists of nanostructured microtubules, we have postulated that neurons may prefer a more complex surface structure than the smooth surface typical of thin-film microelectrodes. We, therefore, investigated the suitability of a nano-porous silicon surface layer to increase the biocompatibility of our thin film ceramic-insulated multisite electrodes. In-vitro testing demonstrated, for the first time, decreased adhesion of astrocytes and increased extension of neurites from pheochromocytoma cells on porous silicon surfaces compared to smooth silicon sufaces. Moreover, nano-porous surfaces were more biocompatible than macroporous surfaces. Collectively, these results support our hypothesis that nano-porous silicon may be an ideal material to improve biocompatibility of chronically implanted microelectrodes. We next developed a method to apply nano-porous surfaces to ceramic insulated, thin-film, microelectrodes and tested them in vivo. Chronic testing demonstrated that the nano-porous surface modification did not alter the electrical properties of the recording sites and did not interfere with proper functioning of the microelectrodes in vivo.