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Paper description: Oxytocin plays its biological role after binding to the oxytocin receptor (OXTR). Genetic variations in the OXTR gene could influence receptor functions, oxytocin binding and effects. The influence of single nucleotide polymorphisms (SNPs) of the OXTR gene (rs53576 and rs2254298) on plasma oxytocin levels and measures of empathy were assessed. This study provides a foundation for a better understanding of the biological basis of empathy and roles of OXTR gene SNPs as “intermediates” of oxytocin effects. Abstract: Oxytocin achieves its effects after binding the oxytocin receptor (OXTR). Oxytocin plays an important role in empathy. The aim of this study was to examine the influence of two single nucleotide polymorphisms (SNPs) of the OXTR gene (rs53576 and rs2254298) on empathy measures and plasma oxytocin levels. Seventy-four university students were screened for the OXTR rs53576 and rs2254298 SNPs using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The level of oxytocin in the plasma was measured by the enzyme linked immunosorbent assay (ELISA). All subjects were assessed with the empathy quotient (EQ) questionnaire and Reading the Mind in the Eyes Test (RMET). Subjects carrying the rs53576 GG genotype had a higher EQ score, compared to GA/AA genotype carriers. By gender analysis, significance was reached only in females. Considering the influence of both examined polymorphisms on empathy, participants with the GGGG diplotype had a higher EQ in comparison with GAGG/AAGG carriers. These hormone effects were not correlated with plasma oxytocin levels. This is the first study implying that higher empathy in rs53576 GG genotype carriers may not depend on plasma oxytocin levels, but possibly on the number and function of OXTRs in the brain. https://doi.org/10.2298/ABS181206057B Received: December 6, 2018; Revised: December 13, 2018; Accepted: December 14, 2018; Published online: December 20, 2018 How to cite this article: Basic J, Milosevic V, Stankovic M, Jevtovic-Stoimenov T, Cvetkovic T, Despotovic M, Pavlovic D. The influence of rs53576 and rs2254298 oxytocin receptor gene polymorphisms on plasma oxytocin levels and measures of empathy. Arch Biol Sci. 2019;71(1):159-65.