In this study, we demonstrated that in vivo and in vitro STS treatment elicited a protective effect against the increased oxidative stress seen in H2O2-treated CSMC and in penile tissues of HFD-fed rat with hyperlipidemia and, furthermore, that the activation of Nrf2/HO-1 pathway is involved in this protective process. Here, HMOX1 is linked to hyperlipidemia.