Leptin is associated with body weight (BW) regulation in adults and adolescents. Decrease in adiponectin in obese adults and adolescents may be associated with the development of obesity and insulin resistance. This study investigated the relationship of plasma leptin and adiponectin levels to changes in BW and body mass index (BMI) over five years among adolescents in Taiwan. Methods: This was a prospective study involving school adolescents aged 12 to 15 years. Demographic data, anthropometric variables, and blood specimens were collected from 1500 adolescents at baseline. Body height, weight and body mass index (BMI) were evaluated at baseline, and after five years in 580 adolescents. Plasma leptin and adiponectin levels were measured using radioimmune assay (RIA). Results: Baseline serum levels of leptin and adiponectin were higher in girls than in boys. Baseline plasma leptin levels correlated positively, and adiponectin levels negatively with BW and BMI at baseline and after five years. Plasma leptin levels were negatively associated with five-year changes in BW and BMI both in normal-weight boys (β=-0.57, p＜0.01, and β=-0.25, p＜0.001, respectively) and girls (β=-0.28, p＜0.001, and β=-0.11, p＜0.001, respectively). The correlation between plasma adiponectin levels and five-year change in BW and BMI in both genders was not statistically significant. Conclusions: In Taiwanese adolescents, plasma leptin levels were negatively and significantly associated with the changes in BW and BMI during the five-year follow-up period in both genders, but adiponectin levels were not. Such finding suggests that plasma leptin levels may be a negative marker of body weight gain over time.