Background: A pro-inflammatory cytokine called interleukin 6 (IL-6) is important for both autoimmune and chronic inflammation. Objective: This study aimed to evaluate the ability to use serum level of IL-6 in differentiating between inflammatory and non-inflammatory arthritis and to correlate its level with clinical manifestations, disease activity, laboratory parameters, radiological grading and disease severity. Methods: This comparative cross-sectional study was carried out on 60 patients diagnosed as rheumatoid arthritis (RA) (Group I), osteoarthritis (Group II) and psoriatic arthritis (PsA) (Group III) together with 20 apparently healthy volunteers selected as control (Group IV), all were age- and sex-matched. The disease activity score 28 (DAS-28) and disease activity index in PsA were developed to quantify disease activity among RA and PsA patients, respectively. Radiographic changes were evaluated by Larsen score among RA patients and by modified Steinbrocker score among PsA patients. Routine lab work was done and serum IL-6 was measured by ELIZA. Results: Highly statistically significant differences were reported between the studied groups regarding serum IL-6 level (P < 0.05) being higher among patients with inflammatory arthritis than others. Significant positive correlations were found between IL-6 with disease activity and severity parameters among RA and PsA patients. Regarding univariate analysis, among RA patients, it was found that DAS-28 score, disease severity, morning stiffness, number of tender and swollen joints, ESR and radiographic changes (Larsen score) were significantly associated with IL-6.   Conclusions: IL-6 is a strong predictor of disease activity and severity in RA and PsA patients but not in OA patients because it plays an important role in mediating inflammation and joint degradation, therefore monitoring the blood level of this cytokine may be beneficial in determining clinical status.