Abstract Objective: To explore the pathways through which negative body image affects depression in college students and possible means of achieving depression interventions in college populations through the mediating roles of self-efficacy and physical activity, and the moderating role of social support. Methods: The study used a convenience random sampling method to collect data from 600 university students using the Body Image Scale, Self-Efficacy Scale, Physical Activity Scale, General Social Support Scale, and Depression Self-Rating Scale; data analysis as well as Structural Equation Modeling was performed using SPSS and M-plus as well as R software. Results: Body image negatively predicted depression, Body image and physical exercise play a chain mediating role between body image and depression, also social support moderated self-efficacy in predicting the pathway of physical activity effects, as well as physical activity in predicting the pathway of depression effects. Conclusion: The study found that college students' dissatisfaction with their physical appearance may induce depression; physical activity can change the association from body image to depression, in which self-efficacy is an important mediator; and social support moderates adherence to exercise, thus providing an intervention for depression.