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The structural and passive mechanical properties of mesenteric resistance arterioles isolated from 30-wk-old lean and obese mice were assessed using pressure myography, and vessel H<jats:sub>2<\/jats:sub>S levels were quantified using the H<jats:sub>2<\/jats:sub>S indicator sulfidefluor 7-AM. Remodeling gene expression was assessed using quantitative RT-PCR, and histological staining was used to quantify vessel collagen and elastin. Obesity was found to be associated with decreased vessel H<jats:sub>2<\/jats:sub>S concentration, inward hypertrophic remodeling, altered collagen-to-elastin ratio, and reduced vessel stiffness. In addition, mRNA levels of fibronectin, collagen types I and III, matrix metalloproteinases 2 and 9, and tissue inhibitor of metalloproteinase 1 were increased and elastin was decreased by obesity. Evidence that decreased H<jats:sub>2<\/jats:sub>S was responsible for the genetic changes was provided by experiments in which H<jats:sub>2<\/jats:sub>S levels were manipulated, either by inhibition of the H<jats:sub>2<\/jats:sub>S-generating enzyme cystathionine \u03b3-lyase with dl-propargylglycine or by incubation with the H<jats:sub>2<\/jats:sub>S donor GYY4137. 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