To investigate the interaction and skin damage of valsartan with polysorbate 80, the physical mixture of valsartan and polysorbate 80 was prepared and then its adhesion, dispersibility, DSC and skin damage in nude rats were investigated. The physical mixture of valsartan and polysorbate 80 appeared as an aggregated form and could hardly be dispersed in water. The DSC curve showed that physical mixture disappeared the intrinsic peaks of valsartan and polysorbate 80 at about $115^{circ}C$ and $170^{circ}C$, respectively. It appeared a new relatively broad endothermic peak at about $150^{circ}C$, suggesting that valsartan was chemically interacted with polysorbate 80. Furthermore, it induced the severe skin irritation and damage in nude mice. Thus, polysorbate 80 must not be used in the preparation of valsartan-loaded pharmaceutical dosage forms.