Abstract: Objective To observe the effects of trimetazidine (TMZ) preconditioning on endothelial cell injury and oxidative stress in rats with acute renal ischemia-reperfusion. Methods 90 SD rats were randomly divided into A and B groups. Group A was given TMZ at a dose of 10 mg/kg. After lavaged for 5 days, ischemia-reperfusion injury (IR1), ischemic postconditioning (IPO1), sham operated (S1) were established. In the same way, the IR2, IPO2 and S2 were established in group B after 5 days of saline enema. The levels of serum creatinine (SCr), urea nitrogen (BUN), vascular cell adhesion molecule 1 (VCAM-1), malondialdehyde (MDA) superoxide dismutase (SOD) were measured at 0, 6, 12, 24 and 48 h after the last recovery of kidney blood supply in each group. Results Compared with IR1 group, the levels of VCAM-1, MDA at 6 h and BUN, SCr, VCAM-1, MDA and renal tubular injury score at 24 and 48 h in IR2 group were significantly higher than those in IR1 group, while SOD was decreased; Compared with IPO1 group, the levels of VCAM-1 and MDA at 6, 12 and 24 h and BUN, SCr and renal tubular injury score at 24 h in IPO2 group were significantly increased, while SOD was decreased at 6, 12 and 24 h; Compared with IPO1, apart from SCr, the levels of BUN, VCAM-1, MDA and renal tubular injury score at 24 h in IR1 group were increased and the levels of VCAM-1, renal tubular injury score at 48 h in IR1 group were significantly increased, and SOD was decreased at both time points; Compared with IR1 group, the levels of VCAM-1, MDA and renal tubular injury score at 12 and 24 h in IPO2 group were increased, while SOD were decreased and apart from MDA, the levels of BUN, SCr, VCAM-1 and renal tubular injury score at 48 h in IPO2 group were significantly increased, while SOD was decreased (P>0.05). Conclusions Compared with IPO alone, using TMZ can reduce the oxidative stress response and decrease the serum VCAM-1 level before the occurrence of IR in rats.