Africa is endemic to the human immunodeficiency virus, acquired immunodeficiency syndrome(HIV/AIDS). In rural settings, the use of orthodox medicine with herbal medication is common. The efficacy of highly active antiretroviral therapy (HAART) has led to increased demand for its therapeutic use although reported to induce structural abnormalities in testicular tissues among other complications. Jatropha tanjorensis (JT) leaf has been reportedly for its numerous benefits which include; antioxidant, anti-anemic and spermatogenic potentials. This study investigated the alterations in testosterone and testis microstructure following the administration of HAART(Zidovudine, Lamivudine and Levirapine [ZLN]), JT ethanolic leaf extract and the concomitant administration of ZLN and JT using in vivo model. Twenty male Wistar rats weighing 163-267 g were allotted into 4 groups of 5 rats per group. Animals were fed with growersâÂÂÂÂÂÂÂÂpellet and provided water ad libitum. Group 1 served received placebo; group 2 received JT 670.8 mg; group 3 received ZLN 9.285 mg while group 4 received a combination of JT 670.8 mg and ZLN 9.285 mg per kg body weight respectively. All administrations were performed via oro-gavage for 7 days. On day 8, animals were humanely sacrificed under chloroform inhalation; with blood obtained for hormonal assay while the testes were harvested, weighed and processed for routine histology. Testicular histo-architecture revealed mild distortions in the seminiferous tubules of test groups, with significantly (p<0.05) increased testosterone compared to control. In conclusion concomitant administration of ZLN and JT possess testiculo-toxic potential.