There is growing evidence on the positive effects of 453 nm blue light in the treatment of chronic inflammatory skin diseases such as psoriasis vulgaris (PV) and atopic dermatitis (AD). The purpose of this study was to investigate the biological effects of blue light on inflammation and skin barrier recovery following acute perturbation with tape stripping and histamine iontophoresis. Skin perturbation, performed on the forearm of 22 healthy volunteers, was repeated twice over two consecutive weeks. In one week, tape stripping and histamine iontophoresis were followed by irradiation with a 453 nm narrow-band LED light source in either continuous or pulsed mode (10 mW/cm2 average irradiance, 200 mW/cm2 peak irradiance). In the other week (control), no light was used. Skin reactions were evaluated up to 72 hours thereafter using transepidermal water loss (TEWL), reflectance spectroscopy and measurement of skin surface biomarkers. At 24 hours after tape stripping, upregulation of interleukin-1α (IL-1α) from baseline was measured in the non-irradiated control (p=0.029). In contrast, no upregulation emerged in the irradiated location (p>0.05). At 24 hours, the irradiated site also displayed higher TEWL than the non-treated control (p=0.034). The b* value (reflecting changes in pigmentation) was higher at 72 hours post light exposure compared to control (p=0.018). At 30 minutes after histamine iontophoresis and following light treatment, a trend towards a higher a* value (reflecting hemodinamic responses) was observed (p=0.051). We provide the first, in vivo evidence that blue light at 453 nm exerts biological effects on acutely-perturbed healthy human skin. The findings about IL-1α and TEWL suggest a conditioning effect of 453 nm blue light on epidermal cytokines and skin barrier formation, which could be linked to the positive outcomes of blue spectral band on inflammatory skin diseases involving an impaired skin barrier, such as PV and AD.