The main findings of our study are: (1) HFD-induced obesity resulted in impaired glucose tolerance and dyslipidemia in both WT and TKO; (2) Deleting TXNIP prevented HFD-impaired vascular recovery following hind-limb ischemia; (3) HFD triggered systemic and local infiltration of CD68+ macrophages to ischemic limb in WT but not TKO; (4) TXNIP deletion prevented HFD-mediated inflammasome activation and oxidative stress; (5) HFD did not affect VEGF level but impaired VEGFR2 activation in WT following hind-limb ischemia. Here, TXNIP is linked to Obesity.