Neuropathic pain is chronic pain that disrupts a patient’s normal life and causes enormous suffering. Fargesin (Far), a product derived from Mulan, has been discovered to exhibit regulatory functions in multifarious diseases. However, the regulatory impacts and related pathways of Far in neuropathic pain progression remain unclear. In this study, following lipopolysaccharide (LPS) stimulation, cell viability decreased, but was reversed by Far treatment (10, 20 and 40 µM). LPS alleviated M2 polarization, but Far addition offset it. Additionally, Far facilitates gene expressions associated with M2 polarization. Lastly, LPS treatment triggered the nuclear factor kappa-B (NF-κB) pathway, but this change was rescued by Far addition. In conclusion, Far promoted LPS-alleviated microglial M2 polarization and relieved neuropathic pain through retarding the NF-κB pathway. This study may provide novel perspectives on Far in neuropathic pain treatment.