OBJECTIVE: This randomized controlled study tested the effect of interoceptive exposure on anterior insula function and connectivity for the extinction of palatable and rotten food-cue associations in adolescent girls with low weight eating disorders (LWED). METHOD: A food-related conditioning paradigm was performed by 39 adolescent girls with LWED and 19 matched controls during functional magnetic resonance imaging (fMRI). Adolescents with LWED were then randomized to 6 sessions of either interoceptive exposure (n = 18) or family-based (n = 21) treatment, followed by a second functional magnetic resonance imaging scan. Whole-brain activation and insula-driven connectivity for the extinction of palatable and rotten food-cue associations were compared between groups, and changes over treatment were compared between the 2 therapies. RESULTS: Adolescents with LWED exhibited diminished bilateral anterior insula activation for the extinction of palatable food-cue associations compared with controls (t = 3.9-4.1, p < .001; Hedges g = 0.47-0.55). Brief interoceptive exposure treatment increased left anterior insula activation for the extinction of palatable food-cue associations (t = 5.10, p < .001; Hedges g = 1.59) and nonsignificantly improved palatability ratings for these associations during extinction compared with family-based treatment (β = -1.492, p = .087). There were no effects of group or therapy on connectivity or activation for rotten food-cue associations. CONCLUSION: These results suggest that targeting food avoidance in adolescent girls with LWED using interoceptive exposure engages anterior insula regions that mediate the visceral sensation of disgust and may underlie the resistance to extinction. The findings present a window into possible pathophysiological mechanisms of anorexia nervosa and other LWED.