To explore a method of establishing mice model with calcium-oxalate kidney stones so as to provide the reliable animal models for follow-up study on pharmacodynamics. Methods: Mice were divided to normal group (A group), model group (B group) and model group (C group) randomly. 075% ethylene glycol and 075% ammonia chloride mixture were administrated orally1 mL/time and 3 times/day to B group mice for 28 consecutive days. 1% ethylene glycol and 1% ammonia chloride mixture were administrated orally to C group mice as well as B group. The same volume of normal saline was administered in parallel to A group. Food and water intake, vital signs, behavior and change of hair were observed in experiment. 24 h urine of mouse was collected for detecting concentration of oxalic acid and calcium at 7, 14, 21, 28 days after modeling. All of mice were sacrificed at the last time, and took the kidney to carry out pathological observation. Results: The phenomenon of inability to crawl on the hind legs, loss of appetite and the dull hair were observed in B and C group mice after modeling 3 days. The situation of C group was more serious than B group. The model animals began to die after modeling 7 days and the mortality rate of C group was higher than that of group B. The concentration of oxalic acid and calcium in urine of B group or C group were more than A group (P<001). The concentration of oxalic acid in B group was significantly higher than that in C group(P<005~001), but the calcium concentration was significantly lower than that of the C group(P<001). No abnormalities and Calcium oxalate crystal were found in the kidney of A group mice. In B and C groups, the renal tissues of mice were swollen. The renal tubular lumen showed obvious expansion, degeneration necrosis and there was obvious chronic inflammatory cell infiltration in renal interstitial. The surface of the kidney is dotted with white crystals or calcification. There are large tracts of crystal in the proximal and distal tubules and Number of crystals in B group was more than that in C group. Conclusion: It was found that 075% ethylene glycol and 075% ammonia chloride mixture can be successfully induced low mortality, high stone rate of calcium oxalate kidney stones in mice.