Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and antibiotics are often used to control inflammation. However, because of side effects such as gastrointestinal issues and immune suppression, there is growing interest in natural treatment candidates capable of reducing inflammation with minimal side effects. Nisin, a bacteriocin, which is made by Lactococcus lactis, has been safely used for many years as a food preservative and has also been found to have anti-inflammatory effects. In this study, the THP-1 human monocytic cell line, commonly used cell line to model inflammation in the lab, was used to investigate the effect of nisin on the cells. These cells can differentiate into macrophages, a type of immune cell, and can take on either a pro-inflammatory (M1-like) or anti-inflammatory (M2-like) form depending on the signals they receive. The THP-1 cells were first turned into resting macrophages (M0-like) by being treated with phorbol 12-myristate 13-acetate (PMA). Then, the cells were exposed to lipopolysaccharide (LPS) to induce M1-like macrophages and treated with nisin at two different doses (25μg/mL or 50μg/mL) for 24 hours. The signal intensity of TNF-α, a marker of M1 macrophages, was detected using immunofluorescence microscopy and the images were analyzed with ImageJ software. Nisin treatment significantly reduced TNF-α levels (p < 0.0001) in THP-1 cells stimulated with PMA and LPS, while those without the nisin treatment displayed high levels of TNF-α. Additionally, the morphology of the nisin-treated THP-1 cells was more elongated and spindle-like, which is typical of M2 anti-inflammatory macrophages. These findings suggest that nisin could be a natural alternative to synthetic anti-inflammatory drugs.