Objective: To assess the serum level of Semaphorin 3A in ankylosing spondylitis (AS) patients and to assess its correlation with disease activity. Subjects and Methods: The study was carried on 40 subjects, 20 AS patients (12 males and 8 females) fulfilled the 1984 Modified New York criteria for diagnosis ofankylosing spondylitis, and 20 healthy subjects, taken as control group (12 females and 8 males). A consent was taken from all subjects to share in the study. Disease Activity Score (ASDAS) was calculated for AS patients and functional assessment was done using the Bath Ankylosing Spondylitis Functional Index (BASFI). Results: Serum levels of Semaphorin 3A were significantly higher(P<0.05) in AS patients more than controls as it ranged between 0.22-31.48 years with a median of 2.93 in AS patients and (0.04-3.91) with the median of 1.83in controls. Also, there was a significant difference(P<0.05) of Serum Semaphorin 3A level in ankylosing spondylitis patients regarding ASDAS CRP score being higher in active AS (ASDAS-CRP ≥1.3) and ranged between (2.17-31.48) vs (0.22- 2.23) in the active vs the inactive AS patients respectively. Serum Semaphorin 3A level (ng/ml) in ankylosing spondylitis patients were significantly correlated with ASDAS- CRP (r=0.82), ASDAS ESR (r=0.76) as p<0.05. Conclusion: Serum levels of Semaphorin 3A were increased in patients with ankylosingsponndylitis and correlated with disease activity. So, Semaphorin 3A can be used as a biomarker for AS disease activity.