Objective To evaluate the effect of tert-butylhydroquinone ( t-BHQ) on DJ-1∕nuclear factor erythroid 2-related factor 2 (Nrf2) pathway during renal ischemia-reperfusion (I∕R) in diabetic rats. Methods Forty SPF healthy adult male Sprague-Dawley rats, weighing 200-220 g, were divided into 4 groups (n＝10 each) using a random number table method: control group (group C), diabetes mellitus group (group D), diabetes mellitus plus renal I∕R group (I∕R group) and t-BHQ group (group T). Diabe-tes mellitus was induced by intraperitoneal streptozotocin 60 mg∕kg and confirmed by fasting blood glucose level＞16. 7 mmol∕L 72 h later. t-BHQ 50 mg∕kg was intraperitoneally injected in 3 times at an interval of 8 h starting from 24 h before surgery in group T, while the equal volume of normal saline was given instead in D and I∕R groups. Blood samples were collected from the apex of the heart at 24 h of reperfusion for deter-mination of serum creatinine (Cr), cystatin C (Cys C) and β2-microglobulin (β2-MG) concentrations. The rats were then sacrificed, and kidneys were removed for determination of pathological changes of kidneys (with a light microscope) and for detection of the expression of DJ-1, Nrf2 and heme oxygenase-1 (HO-1) in renal tissues (by Western blot). Results Compared with group C, the concentrations of serum Cr, Cys C and β2-MG and pathological scores were significantly increased, and the expression of DJ-1, Nrf2 and HO-1 was up-regulated in D, I∕R and T groups ( P＜0. 05). Compared with group D and group I∕R, the concentrations of serum Cr, Cys C and β2-MG and pathological scores were significantly decreased, and the expression of DJ-1, Nrf2 and HO-1 was up-regulated in group T ( P＜0. 05). Conclusion t-BHQ can at- tenuate renal I∕R injury by activating DJ-1∕Nrf2 pathway in diabetic rats.