Skin reaction to irradiation is a key factor to understand the role of high-linear energy transfer radiation in the treatment of cancer, as well as the tolerance of the damage and the functional changes induced in the contiguous normal tissues. Moreover, low doses of neutron are a potentially dangerous hazard during low earth astronautic orbit missions and aircrew activities. To this purpose, mice skin irradiated with 14 Mev neutrons was studied in term of its genomic response combining cDNA microarrays methodology, to analyze transcriptomic changes, and high resolution Fourier transform-infra red (FT-IR) spectroscopy, to monitor the lipid content and distribution in dorsal skin sections after the neutron irradiation treatment. FT-IR spectroscopy imaging provides both spatial and biochemical information on a micrometric scale without being destructive, thus representing a novel and powerful approach in the context of revealing radiation exposure effects.