Excessive wound exudate in chronic wounds can cause skin maceration to occur around a wound, which may delay healing and lead to other complications. In order to assess possible treatment options with topical therapy there is a need to characterize the permeability of wound and peri-ulcer tissue. Previously we have reported the permeability of a range of chemicals with differing physicochemical properties in human ulcerated and peri-ulcer ischaemic tissue. The findings suggested that wound tissue and peri-ulcer tissue were not representative of normally functioning skin barriers. In the present work we have investigated the permeability of tritiated water in peri-ulcer and whole skin human tissue obtained from clinically diagnosed diabetic ischaemic patients. Permeability data for peri-ulcer tissue was generally higher and more variable than for normal tissue. Histological examination confirmed the breakdown of the skin tissue in the peri-ulcer area and also in the normal skin tissue samples taken from diabetic ischaemic patients. The impaired skin barrier function both in the peri-ulcer and normal tissue may offer opportunities for dermal and transdermal therapies for management of diabetes-related complications.