Background: Lithium is an environmental pollutant.The most important use of lithium is in the pharmaceutical industry. Exposure to the lithium for a long term causes disturbances in the structure and the function of the male reproductive system and sperm. Oxidative stress by increasing free radicals is one of mechanisms that lithium induce some problems in testis tissue. Sperm has an antioxidant system including super oxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) enzymes. This system is able to protect the sperm from oxidative stress. Silymarin، as a potent antioxidant is extracted from Silybum marianum seeds، Which by increasing antioxidant defense system can protect the cells from oxidative stress. The aim of this study was to investigate the protective effect of sylimarin against the harmful effects of lithium chloride on antioxidant enzymes in human sperm. Method: In this study, human ejaculated spermatozoa were used. The sperm samples were washed by human tubal fluid containing bovine serum albumin. The sperm suspensions were divided into five groups (20 million spermatozoa per group ). 1. spermatozoa at 0 hour 2. Spermatozoa incubated for 3 hours (control). 3. Spermatozoa treated with lithium chloride(0.5mM). 4. Spermatozoa treated with silymerin (0.1 mM). 5. spermatozoa treated with lithium chloride+silymerin. The treatments performed for three houres. In order to evaluate the antioxidant enzymes activity, the activity of SOD, CAT and GPX in sperm was assessed. The results was analyzed using one-way ANOVA and p<0.05 was considered significant. Result: Lithium chloride exerts a significant reduction (p<0.001) in the activity of SOD, CAT and GPX enzymes. In the silymarin+lithium chloride group، silymarin could significantly (p<0.05) compensate the toxic effects of lithium chloride compared to the lithium chloride group. In addition, the application of silymarin significantly (p<0.000) increased the activity of the enzymes when compared
