Increased mitogen-activated protein kinase (MAPK) activity has been found in human osteoarthritis (OA). Dual specificity protein phosphatase 19 (DUSP19), a member of mitogen-activated protein kinase (MAPK) phosphatases (MKPs), controls the activity of various MAPKs. This study was aimed to explore the function of DUSP19 during OA pathogenesis. Here, OA and healthy control data were downloaded from the NCBI Gene Expression Omnibus database (GSE57218) VSports手机版. Forty-five patients with OA and 25 healthy donors were enrolled in this study. A rat OA model was induced by anterior cruciate ligament transection. Primary cultured chondrocytes were treated with leptin (10 ng mL(-1)). Cell survival, cell apoptosis and reactive oxygen species (ROS) were identified by CCK-8 and flow cytometry, respectively. In the cartilage of OA patients, DUSP19 was expressed in a lower level than in the cartilage of healthy control. The DUSP19 level was negatively correlated with leptin, which was confirmed by experiments in the rat OA model. Moreover, cell apoptosis and JNK activation in the rat cartilage were increased with the increasing of leptin levels and the decreasing of DUSP19 mRNA levels. In primary culture chondrocytes, exogenous leptin suppressed DUSP19 expression. The ectopic expression of DUSP19 significantly ameliorated leptin-induced apoptosis in damaged chondrocytes, accompanied by the reduced production of ROS. Moreover, the activity of JNK stimulated by leptin was suppressed by DUSP19 overexpression. The present study indicated that DUSP19, a downstream of leptin, inhibited apoptosis of chondrocytes through dephosphorylating JNK. .