Objective: Personality and emotional constructs play a central role in relapse to substance use. The aim of the present study was to evaluate the Relationship between behavioral brain systems in relapse to substance use with mediating role of emotion dysregulation. Method: Using a correlational design, 300 individuals using stimulants referring to the addiction treatment centers of Karaj were selected and completed the scale of relapse to substance use, Jackson’s five factor questionnaire, and the emotion dysregulation scale-short form. Results: The results showed that behavioral activation system (BAS) (t=3.535), behavioral inhibition system (BIS)(t=2.363), and fight-flight-freeze system (FFFS) (t=2.02) had direct effects on relapse to substance use. In addition, emotion dysregulation mediated the relationship between BAS (t=2.514) and relapse to substance use (t=5.453), while it did not mediate the relationships between BIS (0.559) and FFFS (t=0.172) with relapse to substance use. Despite lack of significance of some paths, the model had an acceptable fit. Conclusion: According to the significant effects of behavioral brain systems on relapse to substance use through emotion dysregulation as well as the biological basis of personality and emotion regulation strategies, addiction specialists can reduce the rate of relapse to substance use.