Substance use disorder (SUD) is a chronic relapsing neurophysiological disorder characterized by compulsive drug seeking behavior and continued use in the face of severe consequences. Research into SUD has helped to better clarify its underlying mechanisms and development throughout the years, such as its relationship with dopamine signaling (Volkow and Morales, 2015). Despite extensive research shedding light on the underlying mechanisms of SUDs, particularly in cases like cocaine addiction, the quest for effective pharmacotherapies remains elusive. In recent years, researchers have increasingly focused on exploring alternative therapeutic treatments for SUD. The purpose of this study was to measure the effects of chronic aerobic exercise on cocaine evoked locomotor activity. We additionally assessed for possible disparities between males and females in this effect. To do this, we measured acute locomotion induced by cocaine before and after giving free 24 hr/day access to locked or unlocked running wheels for an extended period. In this present study, our findings indicated that chronic aerobic exercise provided protection against locomotor inducing effects of cocaine, but the effect was exclusive to females. In addition, we found that even after taking away home cage wheels for over a week, female mice with prior exercise experience continued to demonstrate significant reductions in cocaine evoked locomotion