Background: School-based vaccination programs may provide an effective strategy to immunize adolescents against influenza. This study examined whether adolescent attitudes toward influenza vaccination mediated the relationship between receipt of a school-based influenza vaccination intervention and vaccine uptake. Methods: Participants were recruited from 2 counties participating in a school-based influenza vaccination intervention trial in rural Georgia (N = 337). Data were collected from surveys distributed to adolescents at pre- and post-intervention time points and from documents indicating vaccine uptake. Guided by the Health Belief Model and the Integrated Behavioral Model, surveys assessed demographic, behavioral, and psychosocial variables. A mediation analysis was used to test whether changes in psychosocial variables from baseline to follow-up mediated the relationship between study condition and influenza vaccine uptake. Results: Controlling for background variables, step 1 of the mediation analysis revealed a significant relationship between study condition and vaccine uptake (odds ratio = 1.77, p = 0.038). Step 2 of the mediation analysis revealed a significant relationship between study condition and changes in psychosocial variables from baseline to follow-up. Steps 3 and 4 of the mediation analysis revealed that there was full mediation of the relationship between study condition and receipt of an influenza vaccination by intention to receive an influenza vaccination. Conclusion: Findings suggest that the success of our school-based influenza vaccination intervention in increasing vaccine uptake was mediated by adolescents' intention to receive an influenza vaccination. Future influenza vaccination efforts geared toward rural adolescents may benefit from addressing adolescent attitudes toward influenza vaccination, particularly increasing intention to receive a vaccine. (Contains 4 tables.)