Vasoactive intestinal polypeptide (VIP) is a neuropeptide from secretin/glukagon family. Recently, the importance of VIP is becoming more evident, and it is thought that VIP is playing an important regulatory role between neuroendocrine-immune-gastrointestinal systems. In this study, we have tried to evaluate the potential role of VIP in patients with ankylosing spondylitis (AS). In this study, 40 patients (30 male and 10 female) with AS and 40 healthy controls were included. X-ray examinations and scoring of sacroiliac joints of the patients with AS were done according to 1984 Modified New York Criteria for AS. All patients have been assessed with Bath Ankylosing Spondylitis Disease Activity Index. Platelet counts were significantly higher in study group (P < 0.05) in contrast to levels of the hemoglobin. The mean VIP levels were 4.2 ± 1.8 (pg/mL) for study group and 2.8 ± 0.8 (pg/mL) for controls. These results were statistically significant (P < 0.05). There was not any correlation between plasma VIP levels with CRP, ESR, Hb, BASDAI results and radiological scoring of the patients (P > 0.05) in contrast to our expectations. However, platelet counts and VIP levels were correlated significantly (P = 0.03). Our data demonstrate that VIP tended to be high in patients with AS when compared with healthy subjects and correlated with platelet counts significantly, for the first time at the literature. According to this study, VIP may have potential role in the pathogenesis of AS, and it is a potential candidate for many kinds of therapies.