Objective: To determine the relationship between the concentration of CC-chemokine ligand 18 (CCL18) in serum and synovial fluid and the severity of knee joint in patients with osteoarthritis. Methods: This study included 100 patients with knee joint osteoarthritis and 70 healthy controls. Disease severity was assessed using the Kellgren-Lawrence grading system and ELISA was used to assess CCL18 concentration in serum and synovial fluid of the study subjects. Spearman correlation analysis was used to analyze the correlation between serum and synovial fluid CCL18 concentration and correlation between serum and synovial fluid CCL18 and KL classification. Results: The serum concentration of CCL18 in patients with knee osteoarthritis was significantly higher than those in healthy controls [(54.13±8.9) ng/mL vs (38.97±6.9) ng/mL, P<0.001]. The serum concentration of CCL18 in patients with KL-4 was significantly higher than those in KL-3 [(72.26±12.90) ng/mL vs (49.56±10.3) ng/mL, P<0.05]. Patients with grade KL-3 were significantly higher than those with KL-2 grade [(49.56±10.3) ng/mL vs (45.85±8.9) ng/mL, P<0.05]. Patients with KL-4 grade synovium Liquid CCL18 concentrations were significantly higher than patients with KL-3 [(45.43±11.09) ng/mL vs (28.49±7.98) ng/mL, P<0.05]. Patients with KL-3 were significantly more than those with KL-2 [(28.49±7.98) ng/mL vs (27.00±5.43) ng/mL, P<0.05]. Serum CCL18 levels were positively correlated with synovial fluid CCL-18 levels (r=0.425, P<0.001). Serum and synovial fluid CCL18 levels were positively correlated with KL grades (r=0.560, P<0.001, and r=0.525, P<0.001). Conclusion: The concentration of CCL18 in serum and synovial fluid is related to the severity of knee osteoarthritis.