Infection is the leading complication associated with intravascular devices, and these infections develop when a catheter becomes colonized by microorganisms. To combat this issue, medical device manufacturers seek to provide healthcare facilities with antimicrobial medical devices to prevent or reduce the colonization. In order to adequately evaluate these devices, an in vivo model is required to accurately assess the performance of the antimicrobial devices in a clinical setting. The model presented herein was designed to provide a simulation of the subcutaneous tunnel environment to evaluate the ability of an antimicrobial peripherally inserted central catheter (PICC), coated with chlorhexidine based technology, to reduce microbial migration and colonization compared to an uncoated PICC. Three samples of control, uncoated PICCs and three samples of coated PICCs were surgically tunneled into the backs of female New Zealand White rabbits. The insertion sites were then challenged with Staphylococcus aureus at the time of implantation. Animals were evaluated out to thirty days and sacrificed. Complete en bloc dissection and evaluation of the catheter and surrounding tissue demonstrated that the chlorhexidine coated catheter was able to significantly reduce microbial colonization and prevent microbial migration as compared to the standard, un-treated catheter.