The aim of this study was to investigate the effect of UV irradiation on streptozotocin-induced diabetic skin. 42 hairless male mice were divided into three groups of control non-diabetic and with dose of streptozotocin 20 and 30 mg/kg. Both FT-IR and Raman spectra showed considerable changes between the diabetic and non-diabetic mice, as well as after irradiation. The most important changes between healthy and diabetic groups were observed in the reduction of vOH intensity absorption bands (4000-3600 cm -1 ), resulting from dehydration of the skin and hyaluronic acid degradation. The increase of the absorption bands of symmetric and antisymmetric methylene groups in the spectral region 3000-2850 cm -1 is related to the increased lipophilic environment of diabetic mice skin. The intensity of these bands increases further upon irradiation. The characteristic "marker band" for the oxidative stress at 1744 cm -1 , due to malondialdehyde formation, increases upon irradiation and it is higher in diabetic tissues. The absorption bands of amide I at 1650 cm -1 and amide II at 1550 cm -1 shift to higher and lower frequencies, respectively, concerning the production of amyloid like proteins, in agreement with the increase of the lipophilic environment. These shifts are more pronounced in infrared spectra. The band at 1171 cm -1 , assigned to C-O-C vibration, increases upon diabetes and skin cancer development. It is important to notice that the mice who received 30 mg/kg streptozotocin showed high resistance to UV irradiation. It seems that streptozotocin inhibits the free radicals, which are produced by UV radiation, to interact with important biological molecules. The protective role of streptozotocin on diabetic mice skin from UV irradiation are unclear. The above observations were in agreement with clinical and literature data.