Even in modern dermatology clinics, the determination of the severity of ultraviolet (UV)-induced erythema and assessment of individual photosensitivity based on the calculation of minimal erythema dose (MED) is still performed visually, which is subjective, and associated with high variability of the results and frequent errors when it done be untrained personnel. The application of non-invasive quantitaitve methods such as laser fluorescence spectroscopy (LFS) and optical tissue oximetry (OTO) could be a solution of these problems. In is well known that acute UV skin damage is associated with structural alterations, vasodilatation and inflammatory response. Moreover, porphyrins which have well-known autofluorescent properties play a role in the chemoattraction of immune cells to the area of local inflammation caused by UV. Using LFS in the preclinical part of the study on ICR mice (N = 25) time-dependent dynamic changes in the fluorescence parameters of porphyrins were found. Optical parameters were in a good agreement with histological findings. Statistically significant correlation was found between the severity of inflammatory infiltrate and the tissue content index (η) of porphyrins. During the clinical part of the study on healthy volunteers (n = 14) the analysis of endogenous fluorescence and microcirculation characteristics by LFS and OTO revealed the correlation relationship between the intensity of endogenous fluorescence of porphyrins and oxygen consumption with a dose of UV radiation. The correlation of the porphyrins fluorescence with a dose of UV was also demonstrated. Overall results have fundamental value and should be investigated and applied in clinical practice to objectively assess and predict MED. © 2021, Springer Nature Switzerland AG.