Introduction. Autism spectrum disorder (ASD) is a life-long neurodevelopmental condition characterized by impairments in communication, social interaction, restricted interests and repetitive behavior. The aetiology of ASD is poorly understood, evidence indicates that inflammation may play a key role. In individuals with ASD, high prevalence of gastrointestinal (GI) disturbances is reported, that are linked to a low-grade chronic inflammation of the intestinal mucosa. The high mobility group box-1 protein (HMGB1) is an intracellular protein with potent proinflammatory cytokine activity that has been implicated in ASD, as well as in other neurological disorders. The objective of this study was to determine plasma levels of HMGB1 in individuals with ASD and to analyze their association with GI symptoms. Methods. The study involved 31 subjects with low functioning ASD and 16 healthy controls aged 2-22 years. Subjects had a diagnosis of ASD based on the ICD -10 (International Classification of Diseases, 10th edition) criteria. History of GI disorders was collected by a questionnaire, and the score of gastrointestinal dysfunction based of frequency of symptoms was calculated . Plasma levels of HMGB1 were measured by a sandwich enzyme-linked immunosorbent assay (ELISA). Statistical analysis included the Chi-square test and Mann Whitney test. The study was approved by the Ethics Committee of the Faculty of Medicine, Comenius University and University Hospital in Bratislava, Slovak Republic. An informed consent from all the subjects or their caregivers was obtained. The study conformed to the code of ethics stated in the Declaration of Helsinki. Results. Plasma HMGB1 levels were significantly higher in individuals with ASD than in controls (13.8 ±11.7 ng/ml vs. 7.90±4.0 ng/ml, p<0.02). GI problems were significantly more prevalent in subjects with ASD (96.8 %, vs 66.6% of controls). In the subgroup of ASD cases with higher HMGB1 levels (11 ng/ml) a significantly higher percent of subjects (83,3 %) suffered by more severe forms of GI problems, whereas in subgroup with lower levels of HMGB1 (<11 ng/ml) mild forms of GI symptoms prevailed (c2=6.42, df=1, p<0.02) Conclusions. Results of the study support the involvement of the low-grade inflammation in the pathomechanisms of autism, and that inflammatory process may underlie the GI symptoms observed in some subgroups of subjects with ASD. More research is needed in order to specify the role of HMGB1 in the pathomechanisms of the autistic disorders.