Introduction: The immune system?s inflammatory response, driven by pro-inflammatory proteins, protects against external threats. Fear and disgust-inducing stimuli have been linked to immune responses, yet their specific physiological and inflammatory mechanisms in trypophobia remain unclear. This study aimed to elucidate the inflammatory and physiological responses in relation to natural (non-skin) and skin-related trypophobic images. Material and methods: Fifty participants (n 5 50) were recruited for the study, and their sensitivity to trypophobia was measured using the trypophobia questionnaire. Then, participants were randomly assigned to either the skin related or non-skin related visual exposure group and viewed trypophobic images from a computer screen. Blood samples were collected pre- and post-exposure to trypophobic images and analyzed for IL-6 and TNF-á using ELISA and RT-qPCR methods. Results: IL-6 and TNF-á protein levels significantly increased post-exposure, with IL-6 changes varying by stimulus type. mRNA expression showed significant interaction with participants? trypophobia sensitivity scores, suggesting post-transcriptional mechanisms. Heart rate variability (HRV) and heart rate were measured before, during, and after exposure using photoplethysmography. Significant changes in HRV metrics, influenced by stimulus type and trypophobia sensitivity, indicated increased sympathetic and decreased parasympathetic nervous system activity during and after exposure. Conclusions: These findings highlight the role of physiological and inflammatory responses in trypophobia, suggesting immune activation and autonomic nervous system involvement based on stimulus type and individual sensitivity. These findings not only contribute to phobia literature but also shed light on the physiological and immunological changes that take place in the bodies of individuals with high sensitivity to trypophobia.  Kulcsszavak: trypophobia, immune system, inflammation, pro-inflammatory cytokines, heart rate variability (HRV)