To examine the longitudinal associations between depressive symptoms and subtypes of social withdrawal among rural adolescents and to explore the mediating role of negative interpretation bias, this study conducted a two-wave longitudinal survey with a six-month interval among 415 rural adolescents using self-report questionnaires. The results showed that: (1) after controlling for gender and age, depressive symptoms at Time 1 (T1) significantly and positively predicted social avoidance and shyness at Time 2 (T2); (2) negative interpretation bias at T2 played a significant mediating role in the associations between T1 depressive symptoms and T2 social avoidance, unsociability, and shyness; and (3) the effect of T1 depressive symptoms on T2 social avoidance, and the effect of T2 negative interpretation bias on T2 shyness, were significantly stronger among rural boys than among rural girls. These findings support the symptom-driven model of depression among rural adolescents and further extend evidence for the mediating role of negative interpretation bias, offering important implications for promoting social integration among rural adolescents.

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