The present study was conducted to evaluate the protective effect of Spirulina on mycotoxins induced liver damage and oxidative stress in rats. Thirty male albino rats were classified randomly into three equal groups. Group1(normal control): Rats fed with ordinary ration. Group2 (Mycotoxin): Rats fed with ordinary ration only for first 7 days and from day 8 rats fed mixed ration contain 50 gram of grinded plant (total aflatoxins 4.2 ppb) + 50 gram of grinded fish (total aflatoxins 42.14 ppb) + 50 gram of ordinary diet (free of aflatoxins) for 4 weeks. Group3 (Mycotoxin+ Spirulina): Spirulina Platensis (500 mg/kg b.wt/day) was administered orally allover the experimental period (5 weeks). Also, rats were fed on ordinary diet only for first 7 days and from day 8 rats fed mixed ration as that mentioned above in group 2. At the end of the experiment liver tissue specimens were isolated and analyzed for the determination of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), L-malondialdehyde (L-MDA) in addition to intrerleukin-1(IL-1) gene expression and DNA damage. The obtained results showed a significant up-regulation of IL-1 gene expression level and marked increase in SOD, CAT, L-MDA and DNA damage that was indicated by an increase in tail length and tail DNA % in liver tissue of mycotoxin rats group. However, liver GSH concentration was markedly decreased as compared to control group. Spirulina protected mycotoxins induced liver damage in rats caused a significant improvement of all previous parameters and attenuates DNA changes. Conclusively, Spirulina Platensis treatment exerts a protective effect against DNA damage and oxidative stress in liver of mycotoxin intoxicated rats through free radical scavenging and anti-inflammatory activities as well as regenerating endogenous antioxidants defense system mechanisms.