This study was performed to determine Effect of short-term spirulina supplementation on DNA damage after exhaustive exercise in athlete men. Twenty male athletes (aged 21.06±1.02years, weight 65.12±1.83 kg and height 172.25±1.63 cm and BMI 21.73±0.73 kg/m2) in a randomized and double-blind design were allocated in two equal supplement and placebo groups (3g/day spirulina for 14 days). After supplementation, all participants were participated in bruce test. The blood samples were taken in three phases (before and after the supplementation and after the exercise). This experiment used single cell gel electrophoresis including modified comet assay (with FPG and ENDO III enzymes) to detect the oxidative DNA damage induced by exhaustive exercise in athlete blood cells, and the product 8-hydroxy- 2-deoxyguanosine (8-OHdG) of oxdation of DNA, also, the level of MDA, BUN and CK in athlete plasma were observed. The normal data (Mean ± SD) were analyzed by repeated measure ANOVA, Tukey and independent t-test (P≤0.05). The results showed that a 14-day spirulina supplementation hadnÂt significant effect on the damage index of modified comet assay (with FPG and ENDO III enzymes) and the level of 8-OHdG and also the level of MDA, BUN and CK in plasma at rest status (P>0.05). However, exercise-induced decrease of 8-OHdG and the value of comet assay and the plasma level of MDA, BUN and CK in the spirulina group were significantly more in comparison with those in the placebo group (P<0.01). Result of the study indicates that 14-day spirulina supplementation can reduce the production of lipid oxidation and oxidative DNA damage during exhaustive exercise.