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Background and Objective: Although acquired immune deficiency syndrome (AIDS) is a vital medical problem but it is more prominant as a personal behavior social cultural phenomenon. Adolescents have been identified as risk population in immune deficiency virus. Health education is only effective method to prevent AIDS. This study was carried out to determine the effect of educational program on knowledge and health belief model structures about acquired immune deficiency syndrome (AIDS) among high school female student in Isfahan, Iran. Materials and Methods: This quasi-experimental study conducted on 72 female students whom divided equaly into case and control groups. The questionnaire included demographic characteristics, knowledge and health belief model. Educational interventions were performed in lecture and group discussion. Data were analyzed using SPSS-18, paired t-test and independent t-test. Results: There were no significant differences in knowledge, perceived severity, benefits and barrier in two groups before intervention. After intervention, there were significant increases in knowledge, perceived severity, perceived benefits and perceived barriers (P<0.05), in the intervention group, but there was not significant increases in perceived susceptibility. Conclusion: Education based on health belief model can improve knowledge, perceived severity, benefits and barriers in female student. More educational sessions are required for improving perceived susceptibility in high school female students.