The present study aimed to investigate the function and possible underlying mechanism of various concentrations of visceral adipose tissue‑derived serine protease inhibitor (vaspin) on leptin‑induced inflammatory and metabolic responses in rat chondrocytes. Rat articular chondrocytes were isolated and treated with different concentrations of vaspin, which was followed by stimulation with leptin. The expression of genes, secretion of nitric oxide and tumor necrosis factor‑α, and activation of the nuclear factor (NF)‑κB pathway were analyzed by reverse transcription‑quantitative polymerase chain reaction, ELISA and western blotting. The results demonstrated that vaspin inhibited the leptin‑induced upregulated gene expression levels of leptin receptor (OB‑Rb), a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS)‑4, ADAMTS‑5, matrix metalloproteinase (MMP)‑2 and MMP‑9, and the secretion of NO and TNF‑α, in a dose‑dependent manner. The phosphorylation of inhibitor of NF‑κB (IκB), IκB kinase (IKK)α, IKKβ and NF‑κB were also promoted by leptin in the chondrocytes, which were also suppressed by increased concentration of vaspin. Taken together, results demonstrated that vaspin prevented leptin‑induced inflammation and catabolism by inhibiting the activation of NF‑κB in rat chondrocytes.