Background: Cimetidine, a common antpeptic ulcer agent, is well known to be associated with deleterious effects on male reproductive parameters. Ginger rhizome (Zingiber officinale) has been reported to counteract the H2-receptor antagonistic activity of cimetidine. Objectives: The aim of this study is to investigate the role of hydro-alcoholic extract of ginger rhizome on some reproductive parameters and its interaction with cimetidine in male mice. Materials and Methods: The parameters measured were: the number of sertoli cells and leydig cells (by standard histopathological techniques) and serum testosterone (by radio immune assay). Forty adult male mice divided into four equal groups (10 mice for each); the 1st group was left as control, the 2nd group was given hydro-alcoholic extract of ginger rhizome, the 3rd group was given cimetidine, the 4th group was administrated hydroalcoholic extract of ginger rhizome orally at a dose of distilled water, 60,35, 60 and after 15 minutes followed by cimetidine at a dose of 35mg/kg B.W respectively once a day for 38 days of experiment (one spermatogenesis period). Hydro-alcoholic extract of ginger rhizome was prepared by Soxhlet apparatus technique. Results: Treatments with cimetidine alone showed a significant decrease, while with ginger extract alone showed a significant increase in all parameters when compared with the control Omar Salim Ibrahim.et.al., 374 group (P<0.05). While the combination treatment of cimetidine with ginger showed similar results to that of the control group (P>0.05). Conclusion: Hydro-alcoholic extract of ginger could improve the efficiency the reproductive parameters of male mice, and alleviate the possible side effects of cimetidine.