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Both vascular adventitial fibroblasts (VAFs) and urotensin II (UII) play important roles in vascular remodeling diseases, but the mechanism of UII in VAFs is still unclear. UII inhibited miR-124 expression through up-regulating circ0004372 expression, thereby promoting SERTAD4 expression. UII significantly promoted the generation of ROS, MDA and 4-HNE, reduced the activities of SOD, GST and GR, increased Fe2+ concentration and inhibited GPX4 expression through circ0004372/miR-124/SERTAD4. Both UII and ferroptosis inducer Erastin significantly promoted the expression of α-SMA, Collagen I and TGF-β1 in VAFs, but circ0004372 siRNA, miR-124 mimics, SERTAD4 siRNA or Ferrostatin-1 significantly inhibited the effect of UII and Erastin on cell activation. When co-transfected with circ0004372 siRNA and miR-124 inhibitors or miR-124 mimics and SERTAD4 overexpression vector, UII still significantly increased the expression of α-SMA, Collagen I and TGF-β1. After transfection with circ0004372 overexpression vector, miR-124 inhibitors or SERTAD4 overexpression vector and then treating with UII and Ferrostatin-1, the expression of α-SMA, Collagen I and TGF-β1 was still significant; when the circ0004372 overexpression vector and miR-124 mimics or miR-124 inhibitors and SERTAD4 siRNA were co-transfected and then UII and Ferrostatin-1 were added, the expression of α-SMA, Collagen I and TGF-β1 was not significantly increased. Therefore, these results indicate that UII promotes the activation of VAFs through the circ0004372/miR-124/SERTAD4/ferroptosis pathway. [ABSTRACT FROM AUTHOR]