Blood plasma is the most informative body fluid, containing large amounts of substances that are released by active secretion or leakage from tissues and cells. Therefore, plasma changes reflect the body state. To explore changes in plasma during the early life of Wistar-rats, the plasma proteomes of newborn and first-week rats were investigated using liquid chromatography-tandem mass spectrometry. A total of 639 proteins were identified at both developmental stages and 570 proteins were used for quantitative analysis. The plasma of first-week rats, compared to that in newborn rats using label-free quantification, showed that the levels of 42 proteins significantly increased while those of 17 proteins decreased. Plasma proteomic patterns at both developmental stages can be easily separated using differential protein cluster analysis. Using the Ingenuity Pathway analysis tool, some pathways including LXR/RXR Activation, DHCR24 Signaling Pathway, Acute Phase Response Signaling, and Detoxification of Reactive Oxygen Species were significantly enhanced. Over 10 categories related to the development and functions were enriched. Plasma proteomes of first-week rats were distinct from those of newborn rats. These changes would make it easier for newborn rats to survive. This is the first study using liquid chromatography-tandem mass spectrometry to investigate newborn rat plasma proteome changes, providing a basis and clues for studying animal development.