Type 1 diabetes mellitus (T1DM) is associated with increased microvascular complications and is a proinflammatory state. The toll-like receptors (TLRs) are pattern recognition receptors on monocytes and important in atherosclerosis. We have shown increased TLR2 and TLR4 expression on monocytes of T1DM compared with controls. In this report, we tested the surface expression of TLR2 and TLR4 on monocytes of T1DM patients with microvascular complications (T1DM-MV) compared with those without (T1DM) and healthy controls. The study was performed at the University of California Davis. Healthy controls (n = 31), T1DM patients (n = 31), and T1DM-MV patients (n = 34) were included. The TLR2 and TLR4 surface expression was significantly increased in T1DM-MV monocytes compared with T1DM and controls (P < .01). In addition, nuclear factor κB activity and interleukin-1β release were significantly increased in monocytes from T1DM-MV compared with T1DM (P < .005). Thus, we make the novel observation that TLR2 and TLR4 expression and signaling are increased in T1DM-MV compared with T1DM and may contribute to the accentuated proinflammatory state and complications of T1DM.