Modifications of transepidermal water loss (TEWL) of rat and human skin induced by oral administration of ciclosporin (CS) were investigated. The integrity of the cutaneous barrier was evaluated using TEWL measurement which is a relatively simple and noninvasive means of assessing the functional state of the cutaneous barrier. After 12 weeks, the TEWL of treated rats decreased significantly and this difference was still present after the 16 weeks of treatment. In humans, there was a statistically significant decrease of TEWL on both forearm and thigh in CS-treated patients compared to non-CS-treated patients and controls (p < 0.05). These results suggest that CS causes skin modifications, particularly concerning its barrier status. The nature of these skin modifications still remains to be determined.