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Major depressive disorder (MDD) affects approximately 300 million people globally, with over 15% having treatment-resistant depression (TRD). People with depression have elevated levels of pro-inflammatory cytokines, especially tumor necrosis factor alpha (TNF-α). Electrical vagus nerve stimulation (eVNS) is an alternative treatment option that works by reducing cytokine production, but requires surgery and isn’t always effective. As an alternative, I propose the use of focused ultrasound stimulation of the vagus nerve (fVNS), which can be applied non-invasively. Low intensity focused ultrasound stimulation has previously been used to stimulate structures in the brain and peripheral nerves such as the sciatic and abducens. However, it has not been used to excite the vagus nerve. In this study, my colleagues and I used an LPS challenge in rats to induce an inflammatory response. I applied one or three 5-minute pulsed focused ultrasound stimulations to the vagus nerve (250 kHz, ISPPA= 3 W/cm2) and collected blood to analyze the effects of fVNS therapy on cytokine concentrations. Animals that received a single ultrasound application saw an average decrease in TNF-α levels by 19%, similar to electrically stimulated animals, which decreased on average by 16% compared to the control. With multiple applications, fVNS therapy statistically reduced serum TNF-α levels (73% reduction) compared to control animals without any observed damage to the nerve. When I cauterized the vagus nerve, the stimulation no longer had a reduction effect on TNF-α. These findings indicate that focused ultrasound stimulation can excite the vagus nerve and has the potential for use as a non-invasive, lower risk therapy for TRD.