Introduction and objectives: Reports indicated that extract of salvia officinalis has antioxidant andantihistaminic activities and could alleviatenephrotoxicity induced by cisplatin. This study was undertaken to investigate the possible cytotoxic and cytogenic effects of aqueous extract of Salviaofficinalis on different tumor cell lines. Methods: The cytotoxicity of Salvia officinalis extracts were evaluated on two tumor cell lines Rabdomyosarcoma (RD) and Murine mammary adenocarcinoma (AMN3), and one normal cell line, Murine fibroblast (L20B). The cytogenetic effects of the plant extract was studied after estimating the Cytotoxicity concentration 50% (CC50) value, on both tumor cell lines and human blood lymphocytes. Whereas 18 albino mice were used to study the in vivo cytogenic effects of Salvia officinalis afterdetermining its Median Lethal dose (LD50). Results: The aqueous extract of S. officinalis has dose dependant cytotoxic effects on tumor cell lines. The results revealed that high significant cytotoxic effect was seen in highest concentrations on RDtumor cell line and AMN3 tumor cell with CC50 5400 μg/ml and 7810 μg/ml respectively. Salvia officinalis extracts induced a significant increase in L20B cell line proliferation. AMN3 tumor cell line was more sensitive to Cisplatin than RD tumor cell line.The cytogenetic effect of aqueous extracts of S.officinalis showed a significant decrease in mitotic index in all concentrations on both tumor cell lines. The plant extract caused a significant decrease in M.I of human blood lymphocyte at 48 hours.However their cytogenetic effect was less than that of Cyclophosphamide (CP).The LD50 of aqueous extracts of S. officinalis leaves is estimated to be 4361 mg/kg. Cytogenetic studies showed significant decrease in mitotic index in all treated mice. Conclusion:1-Aqueous extracts of S. officinalis hasantiproliferative effects on both RD and AMN3 cell lines. 2-Their cytotoxic activity was more efficacious than Cisplatin. 3-The cytogenic effects of the plant extract were less than that of Cyclophosphamide.