The purpose of this population-based study was to investigate the clinical significance of serum thymus and activation-regulated chemokine (TARC) in children with atopic dermatitis (AD). Between 2003 and 2004, 1359 Japanese children aged 5 years and under were prospectively followed. Serum levels of TARC by using an ELISA in each child were monitored throughout the study period. The first tested year, the mean serum level of TARC in children with sustained AD (mean; 691.7 pg/mL) was significantly higher than that of regressed AD children (569.9 pg/mL), newly developed AD children (380.1 pg/ mL), and healthy children (506.3 pg/mL). The changes of TARC levels in sustained AD children found no significance between 2003 (691.7 pg/mL) and 2004 (682.0 pg/mL). The mean levels of TARC of both regressed AD and healthy children significantly decreased from 2003 to 2004 (644.2 pg/mL to 448.7 pg/mL and 506.3 pg/mL to 442.1 pg/mL, respectively). The mean TARC level of newly developed AD children significantly increased from 2003 to 2004 (380.1 pg/mL to 491.8 pg/mL). We demonstrated strong associations between TARC levels and the natural course of childhood AD. Monitoring serum TARC levels of AD children may be useful for the biological evaluation of AD.