Objective: To explore the relationship between osteoprotegerin(OPG)/ receptor activator of nuclear factor-кB ligand (RANKL) system and the disease activity of ankylosing spondylitis and investigate serum osteoprotegerin and soluble RANKL (sRANKL) in evaluating the disease activity of ankylosing spondylitis. Methods: According to the criterion of Bath ankylosing spondylitis disease activity index and erythrocyte sedimentation rate, 22 ankylosing spondylitis cases with definite activity(A group) were matched with 22 ankylosing spondylitis cases with no evident activity (Q group). Serum OPG and sRANKL levels were determined by enzyme-linked immunosorbent assay. Results: Compared with Q group, a significant increasing level of serum sRANKL and sRANKL/OPG ratio was identified in A group, whereas the levels of serum OPG were comparable between them. Serum levels of sRANKL and sRANKL/OPG ratio were positively correlated with C reactive protein, erythrocyte sedimentation rate, Bath ankylosing spondylitis disease activity index and Bath ankylosing spondylitis functional index. Moreover, according to Youden index of ROC curve, the best cut-off point of serum sRANKL (> 4.76 pmol/l) and sRANKL/OPG ratio (> 0.73) for diagnosing disease activity emerged. The diagnostic sensitivity and specificity of cut-off point of serum sRANKL were 86.4% and 72.7%, whereas that of sRANKL/OPG ratio reached 90.9% and 86.4%, respectively. Conclusion: OPG/RANKL system may be associated with the activity of ankylosing spondylitis. Serum sRANKL/OPG ratio can be a promising clinical index in evaluating the activity of ankylosing spondylitis.