Compared to normal, diabetic skin is characterized by great sensitivity. Oxidative stress is directly involved, contributing to accelerated skin aging, xerodermia and poor wound healing. In the last 10 years, cigarette smoke (CS) exposure has been associated with several skin and dermatological conditions and is directly related to the oxidative stress affecting the skin. However, limited data exist concerning the effect of CS on diabetic skin. Some of the effects of cigarette smoke exposure on the skin of hairless diabetic mice were hereby studied and the potential skin protection by topical applications of Pinus halepensis bark extract was investigated. Female hairless SKH-2 diabetic mice were exposed for 8 days to tobacco smoke and topical applications were performed twice daily. Biophysical parameters such as transepidermal water loss (TEWL), skin elasticity and erythema were measured. In addition, the oxidative stress was evaluated. The results show that diabetes and CS have a synergistic negative action on skin condition, with the development of xerosis and high ROS levels whilst topical applications of Pinus halepensis bark extract protect efficiently the toxic effect of CS on skin, by decreasing skin dryness, oxidative stress and blood glucose levels.