Background: Artesunate is commonly used in malaria therapy. Many antimalarial drugs have been associated with male reproductive dysfunction. The effect of artesunate on male reproductive activities was studied using in–vivo and in-vitro experimental models. Methods: Adult male rats (n=6) were orally given artesunate (2.9 mg/kg body weight) on daily basis for five days. Artesunate (2.9 mg/kg body weight) was administered to another group of rats daily for six weeks, while there was a recovery group of rats too. The control animals received the vehicle only. At the end of the treatment, sperm characteristics, serum follicle stimulating hormone, luteinizing hormone and testosterone levels, testicular and epididymal histology and fertility were assessed. Cultured Sertoli cells were treated with 0.3 μM to 10 μM artesunate for five days after which Sertoli cell viability, double-stranded deoxyribonucleic acid (ds-DNA) integrity and genetic expression of Glial cell line-derived neurotrophic factor (GDNF) and transferrin were assessed. The data were analyzed using Graphpad Instat Statistical software. A probability value of p