Background: Xenoestrogens are widely used environmental chemicals that have recently been under scrutiny because of their possible role as endocrine disrupters. Among them is digoxin that is commonly used in the treatment of heart failure and atrial dysrhythmias. Digoxin is a cardiac glycoside derived from the foxglove plant, Digitalis lanata and suspected to act as estrogen in living organisms. Aim of the work: The purpose of the current study was to elucidate the sexual hormonal and biochemical patterns of male albino rats under the effect of digoxin treatment. Material and Methods: Forty six male albino rats (100-120g) were divided into three groups (16 rats for each). Half of the groups were treated daily for 15 days and the other half for 30 days. Control group: Animals without any treatment. Digoxin L group: orally received digoxin at low dose equivalent of 0.0045mg/200g.b.wt. Digoxin H group: administered digoxin orally at high dose equivalent of 0.0135mg/200g.b.wt. At the end of the experimental periods, blood was collected and serum was separated for estimation the levels of prolactin (PRL), FSH, LH, total testosterone (total T), aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), urea, creatinine, total proteins, albumin, total lipids, total cholesterol (total-chol), Triglycerides (TG), low density lipoprotein cholesterol (LDL-chol) and high density lipoprotein cholesterol (HDL-chol). Results: Results showed marked elevation in PRL and FSH levels and significant reduction in LH and total T levels in all treated groups compared to the corresponding controls. Serum enzyme activities (ALT, AST and ALP) and levels of urea, creatinine, total lipids, total-chol, TG and LDL-chol were obviously elevated in all the treated groups as compared to control groups. Marked decline was recorded in the values of total proteins, albumin, A/G ratio and HDL-chol in all the treated groups at the end of the two time intervals of treatment compared to controls. Regarding serum globulin level, treatment of rats with the low dose of digoxin for 15 days induced significant reduction in this parameter, while globulin returned back to its normal level after 30 days of treatment. On the other hand, the high dose of digoxin caused significant decline in serum globulin concentrations at the two time intervals of treatment. Most of the recorded changes in hormonal and biochemical parameters exhibited dose and time-dependent manner. Conclusion: The results of the current research confirmed that digoxin disrupts the sexual hormonal pattern and biochemical parameters. So, we recommend replacing of this drug by others without estrogenic activity, particularly if it is indicated at a high dose or for a long period of time.