Substance abuse among adolescents is an increasing social and medical problem in Egypt especially with lacking of information regarding prevalence and types of abused drugs. Drug abuse in this critical period of testicular development seems to affect fertility. The objectives of this work was to study the prevalence of addicting drugs among adolescent males in secondary public schools and to examine the insult of most prevalent drugs on the fertility of adolescent male albino rats. Participated students were subjected to a structured questionnaire and urine screening for drugs of abuse. The overall prevalence of abused drugs was 13.6%, tramadol was the most (50.5%) followed by cannabis (14.6%). Animal equivalent doses of tramadol & hashish were given orally to 60 male albino rats for 4 months to test their toxic effects on the reproductive system. Significant reduction in testicular weight, relative testicular weight, luteinizing hormone (LH), testosterone in tramadol, hashish groups with the maximum decrease in combined tramadol+hashish group. Degenerative changes with sloughing &disorganization of epithelial cells were detected in H&E stained testicular sections in tramadol & hashish groups, while in the combined group the degeneration was severe with vaculation, interstitial fibrosis, hyalinization and no aggregated sperms in the lumen.It was concluded that the most prevalent abused drugs among adolescents were tramadol, hashish or combination. These drugs have a structural & functional disruption on the reproductive system in adolescent period.