Our study aims to detect whether the serum RANKL could be a novel potential biomarker for activity and diagnosis of rheumatoid arthritis (RA). It included fifty-eight of RA patients and thirty of equal age and sex matched controls. Disease activity was determined by using DAS28-ESR. Serum Levels of RANKL were assayed by ELISA and compared with parameters such as ESR, CRP, Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPA). The serum RANKL levels were higher in RA patients compared to controls. There was an increase in its levels mean among post-menopausal patients compared to post-menopausal healthy group. RANKL levels were also higher in ACPA positive patients than ACPA negative. Our study found a correlation between RANKL levels and some parameters: DAS28, ACPA and symptom duration. No correlation was observed with ESR, TJC, SJC, RF, VAS, CRP. There was a moderate inverse correlation between RANKL levels and BMD. By ROC curve, our results displayed that the best cutoff value of serum RANKL was 178.99 pg/ml (sensitivity 79.31%; specificity 90%) to differentiate between RA patients and controls. In conclusion, elevated serum RANKL can be used as an indicator of disease activity and a diagnostic new biomarker in patients with early RA.