Background: Chemerin is a new adipokine that has been linked to joint inflammation and degeneration. It has a pro-inflammatory effect and modulates immune system activity. Objective: The aim of the work was to assess the chemerin role in diagnosis as well as monitoring severity of the disease in knee osteoarthritis (KOA) patients. Patients and Methods: This case-control study included a total of 60 subjects, 30 of them had knee osteoarthritis (KOA) and 30 served as controls, attending at Department of Rheumatology, Rehabilitation, and Physical Medicine, Zagazig University Hospitals. Chemerin level was measured for all the subjects by ELISA technique. In osteoarthritis group, knee osteoarthritis was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Results: Statistically insignificant differences in age, BMI, as well as sex were found among the 2 studied groups. Serum chemerin levels in patients with KOA were statistically significantly higher than in controls, with a p-value of 0.001. Serum chemerin had no statistically significant correlations to age, BMI, or length of illness, while WOMAC scores, CRP, as well as ESR were strongly associated with serum chemerin levels. Conclusion: It could be concluded that serum chemerin can be utilized as an inflammatory marker in KOA patients and it can be considered as a therapeutic target. Further studies are recommended to assess its levels in other types of OA, and other rheumatic diseases.