Objective To investigate the effects and possible mechanism of Fructus lycii on renal calcium oxalate stone formation in rats. Methods Wistar rats were divided into several groups according to different stone inducer (cigarette smoking, ethylene glycol solution drinking or combination of both), either Fructus lycii infusion interference or not and different interfering concentrations (10% and 25%). Besides, a blank control group was set. After treatment for 40 d, 24 h urine was collected, and renal tissue samples were obtained. The concentrations of calcium, oxalate and citric acid in urine were measured. The deposit condition of calcium oxalate crystals in nephric tubules was observed and scored. The levels of malondialdehyde (MDA) and activity of total-superoxide dismutase (T-SOD) in renal tissues were detected. Apoptosis cells in kidney were observed with TUNEL staining, and index of apoptosis was calculated. Results Compared with blank control group, the urine calcium concentration in group of combination of cigarette smoking and ethylene glycol solution drinking were significantly higher (P<0.01), the scores of calcium oxalate crystals in renal tubules, the levels of MDA in renal tissues and the index of apoptosis of renal tubule epithelial cells in groups of ethylene glycol solution drinking and combination with smoking were higher, while the concentrations of citric acid in urine and activity of T-SOD in renal tissues were lower. Ten percent and 25% Fructus lycii infusion significantly decreased the urine concentrations of calcium in group of combination of cigarette smoking and ethylene glycol solution drinking (P<0.01), decreased the scores of calcium oxalate crystals in renal tubules, the levels of MDA in renal tissues and the index of apoptosis of renal tubule epithelial cells in groups of ethylene glycol solution drinking and combination with smoking, and increased the concentrations of citric acid in urine and activity of T-SOD in renal tissues. There was no significant dose-effect relationship between two concentrations of Fructus lycii infusion. Conclusion Fructus lycii infusion can effectively inhibit the formation of renal calcium oxalate stone in rats with smoking and/or ethylene glycol drinking by reducing the free radicals and apoptosis of renal tissue, decreasing the concentration of elements for stone formation and increasing the concentration of elements for inhibition of stone formation in urine.