Human blood plasma proteome reflects physiological changes associated with a child’s development as well as natural progression of childhood diseases, such as Type 1 Diabetes (T1D). While age-specific normative values are available for proteins routinely measured in clinical practice, there is paucity of comprehensive longitudinal data regarding changes in human plasma proteome during childhood. We applied TMT-10plex isobaric labeling-based quantitative proteomics to longitudinally profile the plasma proteome in 10 healthy children and 11 T1D patients during their development, each with 9 serial time points from 6 months to 15 years of age. In total, over 2000 protein groups were identified at peptide and protein level false discovery rate of 1% and with at least two razor and unique peptides. The longitudinal expression profiles of these proteins were statistically modeled and their temporal changes were categorized. The patterns and relative abundance of proteins obtained by LC-MS were also verified with ELISA. Oxidative stress related proteins have consistently different dysregulated patterns in T1D group than in age-sex matched healthy controls, even prior to appearance of islet autoantibodies – the earliest sign of islet autoimmunity and pancreatic beta cell stress. Our work represents one of the most comprehensive longitudinal profilings of pediatric plasma proteome to date. The temporal profiles of plasma proteome obtained in this study provide a detailed look of the systemic changes of plasma proteome during the natural progression of T1D and also offer a comprehensive resource and reference for biomarker studies in other childhood diseases. Our results also suggest using strictly age-matched clinical samples in a cross-sectional study in pediatric population.