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Background: Recently, we reported synthesis and neuroprotective activity of some new 1,2,4-triazine derivatives against H2O2 and β-amyloid toxicity in two neurotic cell lines, SHSY5Y and PC12. Methods: The promising results obtained prompted us to further study on these potent neuroprotective agents. In the current study, in vivo anti-inflammatory effect and also genoprotective activity of these compounds in endosulfan-mediated toxicity were investigated. Compounds RT and SMO exhibited high anti-inflammatory effect at 3 and 4 hours after injection in 20 mg/kg, and were even more effective than Indomethacin (20 mg/kg). Results: Interestingly, compound SMO in 200 μM was the best compound in reducing micronuclei significantly (P value <0.0001) in lymphocytes treated with endosulfan compared to control group. Conclusion: Herein, we report SMO as a genoprotective agent and a new drug candidate for endosulfan mediated toxicity.