The predominant pathological manifestation of osteoarthritis (OA) is articular cartilage damage. Chondrocytes are the only cell type present in articular cartilage. The proportion of chondrocytes inflammation and apoptosis correlated significantly with the degree of articular cartilage degeneration and progression of OA. Irisin is released from myocytes during physical activity, and acts as a link between muscles and other tissues and organs. Many studies have confirmed the multifunctional role of Irisin and the beneficial effects of this molecule on bone development and regeneration. Little is known about the mechanisms of Irisin on chondrocytes and the development of OA. This study aimed to investigate the mechanisms and effects of Irisin on interleukin-1β (IL-1β)-induced rat chondrocytes. Our results revealed that Irisin improved IL-1β-induced growth inhibition in chondrocytes and attenuated the production of reactive oxygen species (ROS). And Irisin decreased the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and exerted anti-apoptotic effects by the extracellular signal-regulated kinases (ERK) signaling pathway. In conclusion, Irisin acts through the ERK signaling pathway to protect against IL-1β-induced chondrocytes injury by reducing excessive ROS, inhibiting inflammation and apoptosis. The present study sheds new light on the chondroprotective actions of this myokine, and further develops the therapeutic targets of Irisin for bone and cartilage disorders including OA.