Objective To investigate the effect of dexmedetomidine (Dex) on acute renal injury (AKI) in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (CPB) and potential mechanism. Methods EEighty patients, aged 42 to 76 years old, weighing 50−85 kg and regardless of sex, who were scheduled for coronary artery bypass grafting with CPB were enrolled. According to the random number table method, they were divided into two groups (n=40): a control group (group C) and a Dex group (group D). Before anesthesia induction, group D was intravenously injected with a loading dose of 0.6 μg/kg Dex, followed by after 15 min continuous intravenous pump infusion at a rate of 0.5 μg·kg−1·h−1 until 24 h after operation. Meanwhile, the same volume of normal saline was given to group C in the same way. Their heart rate, mean artery pressure (MAP), central venous pressure (CVP) and urine volume were detected before induction of general anesthesia (T0), after surgery (T1), and 24, 48 h and 72 h after operation (T2, T3, and T4). The levels of serum creatinine (Cr), urea nitrogen (BUN), interleukin (IL)‑1β, tumor necrosis factor (TNF)‑α and the percentage of toll like receptor (TLR) 3 cells, nuclear factor‑kappa B (NF‑κB) and caspase‑3 protein expression in peripheral blood mononuclear cells (PBMCs) were measured at T0-T4. The incidence of AKI 48 h after operation was recorded in both groups. Results The heart rate and MAP in group D at T1-T2 were lower than those at T0 (P<0.05), and the heart rate in group C at T3-T4 was higher than that at T0 (P<0.05). During T1-T3, the heart rate and MAP in group D were lower than those in group C (P<0.05). For both groups, the levels of serum Cr, BUN, IL‑1β and TNF‑α at T2-T4 were higher than those at T0, while the levels of serum Cr, BUN, IL‑1β and TNF‑α in group D at T3-T4 were lower than those in group C. The percentage of TLR3 cells in PBMCs at T2-T4 in group D at T2-T4 was lower than that at T0 (P<0.05), and the percentage of TLR3 cells in PBMCs in group C at T2-T4 was higher than that at T0 (P<0.05). The percentage of TLR3 cells in PBMCs in group D at T2-T4 was lower than that in group C (P<0.05). For both groups, the expression of NF‑κB in PBMCs at T2-T4 was higher than that at T0, and the expression of NF‑κB in PBMCs in group D at T2-T4 was lower than that in group C. The urine volumes at T1-T4 in group C were lower than that at T0, and the urine volumes at T2-T3 in group D were lower than that in T0. The incidence of AKI in group C was higher than that in group D (P<0.05). No other statistically significant difference was found between the two groups (P>0.05). Conclusions Dex pretreatment can significantly reduce the risk of AKI after coronary artery bypass grafting with CPB, which may be related to the inhibition of TLR3/NF‑κB and its downstream inflammatory mediators.