Osteoarthritis (OA) is the most common form of arthritis worldwide. Excessive production of pro-inflammatory cytokines such as interleukin-1β (IL-1β) plays a key role in the pathogenesis of OA. OA is generally characterized by degradation of extracellular matrixes such as type II collagen and aggrecans mediated by matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS). Ghrelin is a secreted peptide hormone regulating appetite and the distribution and rate of use of energy. However, the physiological and pharmacological roles of Ghrelin on the pathological progression of OA haven’t been reported before. In the current study, our results indicate that Ghrelin reduced IL-1β-induced expression of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 in a concentration-dependent manner. Notably, Ghrelin ameliorated IL-1β-induced degradation of type II collagen and aggrecan. Mechanistically, Ghrelin is able to inhibit the expression of IRF-1 mediated by inactivating the JAK2/STAT3 pathway. However, Ghrelin didn’t have any impact on IL-1β induced activation of p38. Taken together, our findings identify a novel function of Ghrelin on inhibiting the degradation of type II collagen and aggrecan.