The present study was designed to investigate the effect of Andrographis paniculata (A. paniculata) on Cyclophosphamide (CP) induced genotoxicity in mice. A dose of 4000mg/kg A. paniculata was selected for the study. Animals received 14days pretreatment of A. paniculata followed by induction of genotoxicity by CP (40mg/kg) 24 hours before sacrifice. Mice bone marrow micronucleus assay were employed for the study. Results shows the CP induced significantly increased bone micronucleus Polychromatic, Micronucles, Bilobed cells and P/N ratio, however CP decreased Normal cells. Treatment with A. paniculata Results showed that a significant increase normal cells, Decreased in Micronuclei (MN) formation in polychromatic erythrocytes of Micronucles, Bilobed cells and P/N ratio. Micronuclei (MN) formation in polychromatic erythrocytes, produced cytotoxicity in mouse bone marrow cells Pretreatments with A. paniculata , significantly inhibited cytotoxicity in mouse bone marrow cells induced by CP. Our studies revealed that A. paniculata has protective effect against genotoxicity induced by CP.