Clinical evaluation of skin lesions requires precise and reproducible technologies for their qualitative and quantitative assessment. In this study, we investigate the applicability of a custom-built dermatologic OCT system for longitudinal assessment of intradermal volumes in a mouse model. The OCT, based on an akinetic swept laser working at 1310 nm was employed for visualization and quantification of intradermal deposits of three different hyaluronic acid-based hydrogel formulations-one commercial and two test substances. Hydrogels were applied in 22 BALB/c mice, and measurements were performed over a six-month time period. All hydrogels increased in volume within the first weeks and degraded steadily thereafter. The half-lifes of the test hydrogels (27.2 ± 13.6 weeks for Hydrogel 1, 31.5 ± 17.2 weeks for Hydrogel 2) were higher in comparison to the commercially available HA hydrogel (21.4 ± 12.0 weeks), although differences were not significant. The sphericity parameter was used for evaluation of the deposit geometry. While on the injection day the sphericities were similar (~0.75 ± 0.04), at later time points significant differences between the different test substances were found (T24: PRV 0.59 ± 0.09, Hydrogel 1 0.70 ± 0.11, Hydrogel 2 0.78 ± 0.07; p ≤ 0.012 for all pairs). This study shows the applicability of OCT imaging for quantitative assessment of the volumetric behavior of intradermal deposits in vivo. In the field of dermatology, dermatoscopy and histopathology are still considered the gold standard for skin examination. While the dermatoscope provides a high-resolution view of the skin surface in vivo, it does not give any information about deeper layers. Histopathologic specimen, on the other hand, offer the possibility for high-resolution morphological evaluation of all layers of skin tissue but require taking tissue samples, thus being invasive. Novel imaging approaches 1 like high-frequency ultrasound 2,3 (HFUS), optical coherence tomography (OCT) 4,5 , photoacoustic tomography 6,7 (PAT) and photoacoustic microscopy 8 (PAM), reflectance confocal microscopy 9,10 (RCM) or multiphoton microscopy 11,12 (MPM) have gained increased attention, due to their benefits when compared to standard techniques. First and most importantly, they are non-invasive. This enables both, visualization of the unaltered tissue morphology and repetitive measurements of exactly the same