The present study was designed to evaluate some immunological and cytogenetic effects of Plantago lanceolata aqueous extract and cyclophosphamide in albino male mice (in vivo). The immunological parameters were total and absolute counts of leucocytes, phagocytic index of peritoneal cells, total serum IgG level, hypersensitivity reactions (Arthus and delayed type), while cytogenetic evaluations included micronucleus formation in polychromatic erythrocytes of bone marrow ,metaphase index of bone marrow and spleen cells and sperm-head abnormalities. Additionally, a chemical detection of tannins, polysaccharides, glycosides, flavonoids, saponins, alkaloids and terpens in the aqueous extract was carried out.The evaluations included four main parts. In part one, the immunological and cytogenetic effects of the plant aqueous extract and cyclophosphamide were carried out. Three doses (1.5, 3 and 4.5 mg/kg) of the extract and one dose (15 mg/kg) of cyclophosphamide were investigated, in which the meterials were given for seven days (single dose/day) and the evaluation was carried out on day eight. In part two, interactions (pre- and post-treatments) between the ideal dose (1.5 mg/kg) of the extract and cyclophosphamide were evaluated. In part three, the animals were given a single dose of the investigated material in day one, and then they were sacrificed in days 7. The following results were obtained: 1. The chemical detection revealed that aqueous extract was positive for tannins, polysaccharides, glycosides, flavonoids, saponins, alkaloids and terpens. 2. Cyclophosphamide 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 and spermhead abnormalities were observed. The total and absolute counts of leucocytes were also decreased in comparison with negative control animals. 3. The results of parts one, three and four indicated that P. lanceolata aqueous extract modulated the innate and adaptive immune responses positively as compared to distilled water negative and cyclophosphamide positive controls. Similarly, the spontaneous formation of micronuclei and sperm-head abnormalities were significantly decreased. In both cases the effect was a dose-dependent, and the lower dose (1.5 mg/kg) was better than the higher doses (3 and 4.5 mg/kg), and therefore the former dose was considered as an ideal dose in the next experiments. 4. The results of part two confirmed the forthcoming observations, and the ideal dose (1.5 mg/kg) of aqueous extract showed a significant efficiency in protecting the immune system and the genetic make-up from the immune suppressive and mutagenic effects of cyclophosphamide. In this regard, the pre-treatment with the extract was more effective than posttreatment.