Aim of the work: To assess seminal plasma angiopoietin-2 (Ang-2) in fertile and infertile men with varicocele (Vx) and without varicocele (Vx).Patients and Methods: Randomized controlled trial has been designed. Total number of participants were 130 divided into fertile control without Vx (n=30), fertile men with Vx (n=30), oligoathenoteratozoospermia (OAT) men without Vx (n=35) and OAT men with Vx (n=35). Exclusion criteria were; subclinical Vx, history of trauma, radiation, gonadotoxins, hormonal medications, smoking, leucocytospermia, abnormal kariotyping and diabetes. The patients were subjected to history taking, clinical examination, semen analysis and estimation of seminal plasma Ang-2, Malondialdehyde (MDA) and Glutathione peroxidase (GPx).Results: Fertile men demonstarted significant decrease in the mean seminal Ang-2 level compared with infertile men. Fertile men without Vx demonstrated significant decrease in the mean seminal Ang-2 compared with infertile men without Vx. Fertile men with Vx demonstrated significant decrease in the mean seminal Ang-2 compared with infertile men with Vx. Seminal Ang-2 demonstrated significant negative correlation with sperm count, sperm motility, sperm normal forms, seminal GPx and demonstrated significant positive correlation with seminal MDA. Conclusions: Seminal Ang-2 is elevated in infertile cases compared with fertile ones and in men associated with Vx compared with those without Vx. Seminal Ang-2 showed significant negative correlation with sperm count, sperm motility, sperm normal forms, age, seminal GPx and significant positive correlation with seminal MDA.