Silicon has been used as one of the primary substrates for micro-machined intra-cortical neural implants (INI). The presence of various ions in the extracellular environment combined with cellular biological activity establishes a harsh, corrosive environment in the brain for INI, and as such, a long-term implant’s construction materials must be able to resist these environments. We have examined if environmental components could contribute to changes in the material, which in turn may be a contributing factor to the decreased long-term reliability in INI optimal neural recordings, which have prevented clinical use these devices for the last 4 decades. We tested silicon in artificial cerebrospinal fluid (ACSF), Dulbecco's modified eagle medium (DMEM), and H4 cells cultured within DMEM for 96 hours at 37°C as three various physiological environments to investigate the material degradation. We have observed that Si samples immersed in only DMEM and ACSF showed very minor surface alterations. However, Si samples cultured with H4 cells exhibited a large change in surface roughness from 0.24±0.04 nm to 4.85 nm. The scanning electron microscope (SEM) micrographs showed the presence of pyramid shaped pits. Further characterization with atomic force microscope (AFM) verified this result and quantified the severe changes in the surface roughness of these samples. At this initial stage of the investigation, we are endeavoring to identify the cause of these changes to the Si surface, but based on our observations, we believe that the increased corrosion could be result of chemical products released into the surrounding environment by the cells.