Leptin is known to play an important role in the pathophysiology of osteoarthritis (OA). This study investigated whether synovial fluid (SF) leptin level is related to the radiographic severity of OA and its role as a quantitative marker for the detection of OA. SF was obtained from 42 OA patients who underwent knee surgery and 10 who had no abnormality of articular cartilage during arthroscopic examination. The progression of OA was classified by Kellgren-Lawrence grading scale. The concentrations of leptin were measured with commercial enzyme-linked-immunosorbent serologic assay kits. Median leptin concentrations in SF were significantly higher in OA patients (median 4.40 ng/ml; range 0.5-15.8) compared to controls (median 2.05 ng/ml; range 1.0-4.6; P = 0.006). SF leptin levels showed significant difference according to the severity of OA (P = 0.0125). Median SF leptin level was highest in stage IV patients (11.1 ng/ml), which was significantly higher compared to all other groups including controls (P < 0.05). Age showed a significant positive correlation with leptin concentrations in OA patients (P < 0.05), but not in controls. These results demonstrate that SF leptin concentrations were closely related to the radiographic severity of OA, suggesting that SF leptin levels could be used as an effective marker for quantitative detection of OA.