BACKGROUND: Pulsed electromagnetic field (PEMF) is a non-invasive treatment that utilizes electromagnetic fields to reduce inflammation and promote tissue repair. However, PEMFs' anti-inflammatory effect on osteoarthritis (OA) and the potential mechanism has not been fully elucidated. METHODS: Human chondrocytes (C28/I2) were stimulated with interleukin (IL)-1β with or without the treatment of PEMF. CCK-8 assay Kit was used to detect cell viability. RT-qPCR, ELISA, immunofluorescent staining and western blot was used to analyze relative markers of inflammatory response and extracellular matrix (ECM) under the treatment of PEMF and related mechanism. Besides, the significance role of Sirt1 was assessed by using the Sirt1 inhibitor (EX-527). Moreover, immunohistochemistry and immunofluorescence staining were carried out to evaluate the curative effect of PEMF on OA mice induced by the destabilization of the medial meniscus (DMM). RESULTS: PEMF inhibited IL-1β-mediated the expression of pro-inflammatory factors. Besides, PEMF alleviated IL-1β-induced degradation of ECM by increasing the expression of Col2a1 and ACAN, while inhibiting the expression of MMP13 and ADAMTS5. At the mechanism level, PEMF increased the expression of Sirt1 and inhibited IL-1β-induced the activation of NF-κB pathway. Furthermore, blocking Sirt1 with EX-527 attenuated the effect of PEMF on the inhibition of NF-κB pathway and the expression of ECM in IL-1β-induced chondrocytes. In vivo, PEMF-treated OA mice showed low modified mankin scores, reduced the number of osteophytes and preserved joint structure. CONCLUSIONS: Our results suggest that PEMF inhibits NF-κB pathway and blocks the expression of inflammatory factors by activating the expression of Sirt1, which may be a novel strategy for OA.