Recent years have witnessed rapid growth in the area of microneedle-assisted intradermal drug delivery. Several publications involving in vivo studies in humans and minipigs have demonstrated distinct change in pharmacokinetics of peptides and proteins following intradermal (ID) administration as compared to subcutaneous (SC) injections. Specifically, ID administration produced a “left-shift” in pharmacokinetic profiles i.e. shorter time to achieve maximum plasma concentrations (shorter Tmax), and often higher maximum plasma concentrations (higher Cmax), as compared to the SC route. In the present work differences in the kinetics of drug absorption after ID and SC administration were explored for eight peptides and proteins with the focus on obtaining quantitative information about the absorption process and identifying similarities and differences in the absorption behavior across compounds. We confirmed that systemic uptake, as judged by apparent absorption rate constants, was 2- to 20-fold higher from the dermis as compared to the subcutis. Additionally, shapes of time-resolved absorption rate profiles demonstrated notable differences in absorption kinetics between ID and SC routes. For both administration routes evaluated herein there was a general trend of small macromolecules absorbing at higher rates as compared to the large macromolecules.