Purpose: This study was done to investigate the effect of self-esteem on perceived stigma in high school students toward people with disabilities. Methods: The participants in this study were 140 high school students from Gyeonggi Province. Data were collected during May 2013. Structured questionnaires were used for data collection. Data were analyzed using descriptive by statistics, t-test, ANOVA, Pearson correlation coefficients, and simple regression analysis with the SPSS 19.0 program. Results: The major findings of this study are as follows: There was a significant relationship between stigma toward people with disabilities and self-esteem among the high school students (r=-.205, p=.015). There was also a significant relationship between relationships with friends (r=.291, p<.001), health statement (r=.400, p<.001) and self-esteem among the high school students. Self-esteem explained 3.5% of the variance in high school students' stigma toward people with disabilities (F=6.041, p=.015). Conclusion: Findings of this study suggest a need to develop education to increase self-esteem as a strategy to decrease high school students' stigma toward people with disabilities. Also, findings of this study suggest the need for repeated study on the relationship between self-esteem and stigma toward people with disabilities among adults.