Background: Lithium is an environmental pollutant which is used in pharmacy industry. Lithium chloride exerts harmful effects on male reproductive system and human sperm by induction of oxidative stress. Sylimerin as a potent antioxidant extracted from Silybum marianum can reduce the oxidative stress. The aim of this study was to investigate if silymarin can protect the harmful effects of lithium chloride on human sperm motility, viability, total antioxidant capacity and lipid peroxidation. Method: In this study, high quality spermatozoa were used. The samples were washed by human tubal fluid containing bovine serum albumin. The sperm suspensions were divided into 5 groups (2× 10 spermatoza per group). 1. Spermatozoa at 0 hour 2. Spermatozoa incubated for 3 hours (control) 3. spermatozoa treated with lithium chloride (0.5mM) for 3 hours 4. Spermatozoa treated with silymerin (0.1mM) for 3 hours 5. Spermatozoa treated with silymarin+lithium chloride for 3 hours. Sperm motility was performed according to World Health Organization (WHO) guidelines and eosin-nigrosin staining, while malondialdehyde (MAD) and ferric reduceing antioxidant power (FRAP) were assessed to investigate lipid peroxidation and total antioxidant capacity respectively. The results were analyzed using one-way ANOVA and p<0.05 was considered significant. Result: Lithium chloride reduced a significant (p<0.000) in percentage of motility, viability and total antioxidant capacity, while increased (p<0.001) the amount of MAD compared to the control group. In the silymerin+lithium chloride group, silymarin could significantly (p<0.001) reverses the toxic effect of lithium chloride on these parameters, when compered to the lithium chloride group. The application of silymarin alone significantly (p<0.001) increased motility, vaiability, FRAP and decreasesd the amount of MAD as compared to the control group. Conclusion: Lithium choloride by inducing oxidative stress exerts toxic effects on motility, vaiabilit