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Vagus nerve stimulation (VNS) has been on the forefront of inflammatory disorder research for the better part of the last three decades and has yielded many promising results. There remains, however, much debate about the actual biological mechanisms of such treatments, as well as, questions about inconsistencies in methods used in many research efforts. In this work, I identify shortcomings in past VNS methods and submit new developments and findings that can progress the research community towards more selective and relevant VNS research and treatments. In Aim 1, I present the most recent advancements in the capabilities of our fully implantable Bionode stimulation device platform for use in VNS studies to include stimulation circuitry, device packaging, and stimulation cuff design. In Aim 2, I characterize the inflammatory cytokine response of rats to intraperitoneally injected endotoxin utilizing new data analysis methods and demonstrate the modulatory effects of VNS applied by the Bionode stimulator to subdiaphragmatic branches of the left vagus nerve in an acute study. In Aim 3, using fully implanted Bionode devices, I expose a previously unidentified effect of chronically cuffing the left cervical vagus nerve to suppress efferent Fluorogold transport and cause unintended attenuation to physiological effects of VNS. Finally, in accordance with our findings from Aims 1, 2, and 3, I present results from new and promising techniques we have explored for future use of VNS in inflammation studies.