The present study was designed to evaluate the immunological and cytogenetic effects of sage's (Salvia officinalis) leaves extracts (aqueous or hexane) and the anti-leukemia drug cytosar on albino male mice (in vivo). The immunological parameters were total and differential counts of leucocytes, phagocytic index of peritoneal cells, hypersensitivity reactions (Arthus and delayed type) and metaphase index of bone marrow and spleen cells, while cytogenetic evaluations included micronucleus formation in polychromatic cells of bone marrow and sperm-head abnormalities. The assay of micronucleus was further evaluated in blood cultures of acute lymphoid leukemia (ALL) patient cells. Additionally chemical analysis of both extracts were carried out. The evaluations included three main parts. In part I, the immunological and cytogenetic effects of aqueous or hexane extract and cytosar were carried out. Three doses (83.9, 167.8 or 251.7 mg/kg) of both extracts were investigated, while a dose of 1.54 mg/kg of cytosar was tested. In part II, interactions (pre- and post-treatment) between the ideal dose (83.9 mg/kg) of both extracts and cytosar were evaluated. In both cases, the extracts and cytosar were administrated subcutaneously. In part III, included assessments of micronucleus formations in blood cultures of ALL patients and healthy controls after treatments with three concentrations (250, 500 or 1000 µg/kg) of the aqueous extract through direct effect and in interaction with cytosar. The following results were obtained: 1. Chemical analysis revealed that aqueous extract consisted mainly of tannins, glycosides, flavonoids, saponines and terpens, while the hexane extract was mainly contain steroids. 2.Cytosar declared clear immune suppressive and mutagenic effects as judged by the investigated parameters. Reduced indices of metaphase, phagocytosis, Arthus, as well as, delayed type hypersensitivity reactions, and increased frequencies of micronucleus formation (in vivo and in vitro) and sperm-head abnormalities were observed. The results of part I indicated that sage's extracts modulated the innate and adaptive immune responses positively as compared to negative (distilled water and sunflower oil) and positive (cytosar) controls. Similarly, the spontaneous formation of micronuclei and sperm-head abnormalities were significantly decreased. In both cases the effect was a dose-dependent. 4. The results of part II confirmed the observations made in part I, and the ideal dose of aqueous and hexane extracts showed a significant efficiency in protecting the immune system and the genetic make-up from the immune suppression and mutagenic effects of cytosar. In this regard, the pre-treatment with the extract was more effective than post-treatment. 5. The aqueous extract was effective in reducing the frequency of micronuclei, spontaneously formed or induced by cytosar, in blood cultures of ALL patients and controls.