Objective:To observe the effect of Evodiamine (EVO) by inhibiting oxidative stress on kidney function in rat models of renal calcium oxalate stones. Methods:A total of 10 rats were randomly selected from 50 SPF SD male rats as the blank group,and the rest rats were used to establish the rat models of renal calcium oxalate stones by intragastrical administration of 1.25% ethylene glycol + 1% ammonium chloride mixture. After successful modeling, the above rat models were randomly divided into the model group , the L-EVO group , the H-EVO group and the positive group , with 10 rats in each group. The L-EVO group and the H-EVO group were intraperitoneally injected with 40 mg/kg and 80 mg/kg EVO, respectively. The positive group was intragastrically administered with 20 mg/kg Puerarin once a day. All the groups were treated for four weeks. The blank group and the model group were given the same amount of normal saline. The urine and serum biochemical indexes of rats were detected; HE staining was used to detect the pathological changes of renal tissue;the deposition of calcium oxalate crystals was detected by Pizzolato staining. Results:Histopathological examination showed that the staining of renal tissue of rats in the blank group was clear, and there was no calcium oxalate deposition, renal tubular degeneration, necrosis or inflammation, and calcium oxalate crystal deposition. Compared with the blank group, the model group found extensive oxalate crystal deposition in the renal tubules, severe renal tubular degeneration and necrosis,inflammatory cell infiltration into the renal interstitium and the formation of renal tubular cyst. The renal structure in the L-EVO group, the H-EVO group and the positive group was significantly improved when compared with that in the model group. The number of calcium oxalate crystals, and the levels of calcium, oxalate, phosphate, urea nitrogen, urea, uric acid, MDA, TNF- α, IL-1β and calcium oxalate crystal deposition in the model group were elevated when compared with those in the blank group (P<0.05), and the contents of magnesium, SOD and GSH were down-regulated (P<0.05). Compared with those in the model group, the number of calcium oxalate crystals, and the levels of calcium,oxalate,phosphate,urea nitrogen,urea,uric acid,MDA,TNF-α,IL-1β and calcium oxalate crystal deposition in the L-EVO group,H-EVO group and positive group were respectively dwindled (P< 0.05),and the contents of magnesium,SOD and GSH were up-regulated (P<0.05). Compared with those in the L-EVO group, the number of calcium oxalate crystals, and the levels of calcium, oxalate, phosphate,urea nitrogen,urea,uric acid,MDA and TNF-α,IL-1β and calcium oxalate crystal deposition in the H-EVO group were reduced (P<0.05), and the contents of magnesium, SOD and GSH were elevated (P<0.05). Conclusion:EVO can improve the kidney function in rat models of renal calcium oxalate stones by inhibiting oxidative stress.