Objective: To assess serum interleukin-6 (IL-6)level in patients with systemic sclerosis (SSc) and its correlations with European Scleroderma Study Group activity score (EUSTAR), Scleroderma Assessment Questionnaire (SAQ), disability index and cardiopulmonary involvement., Methods: Twenty SSc patients and 10 matched healthy controls were included. Serum IL-6 was measured in patients and controls. Disease activity, status,and disability were assessed.Cardiopulmonary involvement was evaluated by pulmonary function tests (PFTs), six minute walk test, echocardiography, and high resolution computed tomography (HRCT) of chest., Results: Serum level of IL-6 was significantly higher in patients with SSc (6.3± 1.4pg/ml) versus healthy controls (3.2± 0.4pg/ml) (P=0.002). IL-6 level showed positive correlations with disease duration (r=0.49, P=0.03), EUSTAR score (r=0.64, P=0.002), Index of Respiratory Status "IRS" (r=0.46, P=0.001), Index of Musculoskeletal Status "IMSS" (r=0.45, P=0.049), Index of Vascular Status "IVS" (r=0.39, P=0.04), mean and peak of pulmonary artery pressure (r=0.44 & 0.55, P=0.02 & 0.002 respectively). Negative correlations of IL-6 level with DLCO% (r=-0.49, P=0.006),six minute walk distance (6MWD) (r=-0.52, P= 0.003) and right ventricle fraction area change (r=-0.48, P=0.03) were found, while there were strong positive correlations with HRCT-ground glass score (r=0.77, P=0.0001) and HRCT-fibrosis score (r=0.62, P=0.003)., Conclusion: IL-6 level is increased in patients with SSc and significantly correlates with EUSTAR score, IRS, DLCO, 6MWD, HRCT scores, and echocardiographic abnormalities of the right side of the heart. These results support the role of IL-6 in the disease activity and in the development of cardiopulmonary manifestations in SSc patients.