Introduction: Local inflammation is an important regulator of vascular remodeling. We hypothesized that adipose tissue adjacent to hemodialysis arteriovenous fistulae modulates maturation. Methods: During fistula creation, perivenous adipose was collected from 111 participants in the Hemodialysis Fistula Maturation Study. Nine adipose-associated mediators were measured. Duplex ultrasound was performed at 4 time points postoperatively from 1 day to first cannulation (10–26 weeks). Associations between logarithmically transformed biomarker levels and fistula remodeling were evaluated using mixed effects regression. Results: Elevated interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 were associated with a reduction in the fractional vein diameter during the early time frame of 1 day to 2 weeks (diameter change of 26.6% and 20.4% at the 25th and 75th percentile for IL-6, P = 0.01; 27.8% and 21.1% at the 25th and 75th percentile for MCP-1, P = 0.02), but not in later stages of remodeling. Local leptin levels showed a significant negative correlation with fractional venous flow increase between 2 and 6 weeks (percent flow change 31.4% and 11.3% at the 25th and 75th percentile for leptin, P = 0.03). Conclusion: Thus, impaired fistula vein dilation and reduced capacity for flow augmentation associate with specific local adipose phenotypic signatures in a time-dependent manner. In view of adipose tissue plasticity, these findings raise the possibility of novel adipose-based strategies to facilitate fistula maturation. © 2018