BACKGROUND: Systemic sclerosis (SSc) has the highest level of mortality and disability among all rheumatological diseases. Being heterogenous leads to no predictable method for clinical courses. The aim of this study was to evaluate the levels of miRNA-126 and soluble VCAM-1 protein markers in patients with SSc, and to examine the assossiation of their levels with the severity of clinical and paraclinical parameters in patients with SSc. METHOD: In current study tweny six patients with SSc along with twenty-three SSc-free controls were recruited. Enzyme-linked immunosorbent assay (ELISA) was performed to measure the VCAM-1 protein. MiRNA-126 amounts in serum were detected by quantitative real-time polymerase chain reaction (PCR). RESULT: SSc patients' average age was 45.42 years and control group 49.85. The mean±SD for circulating miR-126 levels were significantly lower in SSc patients compared with healthy donors (p = 0.02), 0.48 ± 0.72 vs 1.11 ± 0.61 respectively. A significant difference was also observed in the serum level of miRNA-126 in SSc patients who suffer from pulmonary artery hypertension (P = 0.03) and pulmonary fibrosis (P = 0.04). In contrast, analysis of the serum VCAM-1 levels in the study groups uncovered a significant increase in SSc patients (5.92 ± 3.52 µg/ml) compared to control group (2.62 ± 1.2 µg/ml) (P value <
0.001). CONCLUSION: Significant change in circulating levels of miR-126 and VCAM-1 in the SSc patients supporting its role in the pathogenesis of the disease. It could also proposed potential role as a predictor of pulmonary complications for miRNA-126.