BACKGROUND: Sexual violence, a pervasive global issue, significantly impacts individuals and societies, necessitating a deeper understanding of its underlying biological mechanisms. This study aimed to elucidate the role of stress-induced dysregulation of the hypothalamus-pituitary-adrenocortical axis in sexual aggression in male Wistar rats. Employing a sexual aggression paradigm, we investigated the effects of social isolation on aggression, anxiety-like behaviour, and neurochemistry in virgin adult male Wistar rats. RESULTS: The results showed that social isolation significantly escalated aggressive behaviours and induced anxiety-like responses in male rats. The sexual aggression test revealed that socially isolated males exhibited heightened aggression towards non-receptive females. Neurochemical analyses indicated significant alterations in key markers, such as corticotrophin-releasing hormone, oxytocin, and arginine vasopressin, correlating with the observed behavioural changes. Gene expression analyses revealed significant findings, particularly in the expression of the oxytocin receptor (OXTR) and vasopressin receptor 1 A (AVPR1A) genes. Social isolation and the duration of aggressive behaviour prior to the sexual aggression test significantly influenced OXTR expression in the hippocampus and AVPR1A expression in both the prefrontal cortex and hippocampus, highlighting the complex interplay between environmental stressors, neurochemical responses, and gene expression in the manifestation of sexual aggression behaviour. CONCLUSIONS: This study underscores the critical impact of stress and social isolation on sexual aggression, providing valuable insights into possible neurobiological underpinnings of sexual violence. Understanding these mechanisms is crucial for developing effective interventions to mitigate the consequences of sexual aggression.