: The effects of long-term ingestion of fluoxetine on fertility were investigated in Sprague-Dawley male rats. Adult male rats were exposed to fluoxetine at a concentration of 200 mg/kg for 60 days. Long-term ingestion of fluoxetine for 60 days caused a great decrease in spermatogenesis in seminiferous tubules of the testes. Sperm motility and density were also significantly reduced in cauda epididymides and testes of the treated group. The weights of reproductive organs (testes, epididymides, ventral prostrate and seminal vesicle) were decreased considerably. The hormonal assay also showed significant decrease in testosterone levels and FSH levels. Testicular cell population dynamics also demonstrated a decrease in the number of both primary and secondary spermatocystes and spermatids in the treatment group. The number of female rats impregnated by male rats on long-term fluoxetine diet had decreased. The number of implantations and the number of viable fetuses were also notably decreased in female rats impregnated by male rats ingested fluoxetine. Fluoxetine caused a slight decrease in body weight, when initial and final body weights were compared in the experimental groups. Levels of ALT and AST were found to be significantly increased in the treated group when compared to the control. Histometery of reproductive organs confirmed these results. In conclusion, these results confirm that the long-term fluoxetine ingestion produce adverse effects on fertility and reproductive system in adult male rat. Thus, it would be of great interest to investigate the impact via long -term treatment with fluoxetine in male human fertility.