To examine the effects of zinc gluconate (ZG) on the nephrotoxicity of cis-platin (CDDP), changes in renal function and glutathione metabolism were investigated in mice. Fifty mice were randomly divided into five equal groups: controls, CDDP group and three ZG plus CDDP groups; the dose of ZG was 100 mg, 140 mg and 180 mg/kg respectively. Mice were sacrificed after 48 hours of CDDP (9 mg/kg) treatment; the levels of serum creatinine (Cr) and blood urea nitrogen (BUN) were measured, the glutathione (GSH) and malondialdehyde (MDA) content and the activities of glutathione peroxidase (GHS-PX) and catalase (CAT) in whole blood and renal tissue were assayed. Compared to the control group, there were significant increases in Cr, BUN and MDA, and decreases in the activities of GSH-PX in the CDDP group in whole blood and renal tissue. Preadministration of ZG at the doses of 140 mg/kg and 180 mg/kg significantly increased the concentration of GSH in whole blood, and decreased the levels of Cr and BUN, and the MDA content in whole blood and renal tissue, compared with the CDDP group. We conclude that preadministration of ZG might improve renal function and glutathione metabolism and reduce the nephrotoxicity of cis-platin.