Although the etiopathology of autism spectrum disorder (ASD) is not clear, immune dysfunction has been proposed as a mechanism for the pathophysiology of ASD. The purpose of this study is to examine serum levels of tissue plasminogen activator (t‐PA) and some adhesion molecules in children with ASD that have not been investigated previously in detail. The study group included 35 male children aged from 2 to 9 diagnosed with ASD according to DSM‐V criteria. Soluble platelet endothelial adhesion molecule‐1 (sPECAM‐1), P‐selectin, E‐selectin, and t‐PA in the serum were determined with enzyme‐linked immunosorbent assay. Autism behavior check list (ABC) is used for the assessment of ASD severity. The levels of t‐PA (P = 0.025) and E‐selectin (P = 0.007) was detected significantly higher in children with ASD than control group. Serum levels of sPECAM‐1 showed statistically significant negative correlation with sensory, body and object‐use, language, social, and self‐help and total scores in the patient group (r = −0.349, P = 0.04; r = −0.411, P = 0.01; r = −0.412, P = 0.01; r = −0.417, P = 0.01, and r = −0.531, P < 0.01, respectively). Serum levels of P‐selectin levels showed statistically significant negative correlation with ABC total score in the patient group (r = −0.378, P = 0.03). It may be suggested that t‐PA, E‐selectin, P‐selectin, and sPECAM‐1 a crucial role in inflammatory conditions in children with ASD. Autism Res 2016, 9: 1241–1247. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.