Background: Polycystic ovarian syndrome (PCO) is a syndrome of ovarian dysfunction with polycystic ovary morphology and features of hyperandrogenism. Aim of work: This work aimed to compare the histological effects of adipose-derived stem cells (ADSC) to clomiphen on the treatment of letrozole experimentally-induced polycystic ovary in rats. Materials and methods: 50 adult female albino rats were divided into: Group I (control), group ІІ (PCO group) that received Letrozole for 21 days. Then 5 rats from each group were sacrificed to prove PCO. Remaining 20 rats of PCO group were subdivided: Subgroup ІІB (Recovery group), Subgroup ІІC (clomiphene-treated group), Subgroup ІІD (ADSCs-treated group), Subgroup ІІE: (clomiphene + ADSCs treated group), while the control group was subdivided into subgroups IB, IC, ID and IE, that received the solvents for 3 more weeks as in the corresponding subgroups in G II. Ovarian specimens were processed and stained with H and E, Periodic acid Schiff (PAS) reaction, immunohistochemichal stain using Ki 6. Morphometric and statistical analyses were done. Results: PCO group showed dilated ovarian cysts, thinned granulosa layer, cell debris appeared in the follicular cavity. Clomiphen and ADSC improved the ovarian histological architecture where various stages of ovarian follicles were noticed, including corpora lutea and few cysts. Conclusion: Clomiphen effect was found to be comparable with ADSC effect , while combining ADSC + Clomiphen gave the best results.