There is an accumulation in studies which strive to reveal zonulin's potential role in mental disorders. To date, one cross-sectional recent study examined zonulin in patients with bipolar disorders (BDs); however, its role still remains vague due to high fluctuation. Our aims are to determine plasma zonulin levels in exacerbation and treatment response periods, and to examine the associations between zonulin and symptom severity in BD. 30 patients with BD type I and 29 healthy controls participated in the current study. Socio-demographic form, Young Mania Rating Scale (YMRS), and Hamilton Depression Rating Scale (HAM-D) were administered. Enzyme-linked immune assay (ELISA) method was used to measure the plasma zonulin levels of the participants. The groups did not differ in plasma zonulin-level comparisons. Plasma zonulin did not alter between the exacerbation and treatment response periods of the patients. Besides, no associations were found between plasma zonulin-level and disease symptoms. Intestinal barrier integrity was not found to be altered among patients with BD type I. The lack of alterations in plasma zonulin level between different periods may be attributable to several factors. One possible factor might be the ELISA method which can detect other proteins (e.g., properdin) rather than zonulin. Therefore, it might fail to indicate direct observation of intestinal permeability. However, future study designs with more accurate estimation of zonulin in a larger sample may provide a different perspective on intestinal permeability's possible role in BD etiology.