Introduction: Skin photoaging is characterized by coarse wrinkles, loss of elasticity and dryness. The worst scenario of ultraviolet (UV) ray exposure can reach up to skin malignant changes. The topical application of growth factors has proven to be effective in ameliorating the photoaging. Among the paracrine products of stem cells are exosomes which also play an important role. Aim of the Work: To investigate the effect of exosomes derived from adipose mesenchymal stem cells on the histological structure of photoaged rat thin skin versus topically applied growth factors. Materials and Methods: Forty-five young adult male albino rats aged between 6 - 8 weeks were used in this study. Animals were subjected to gentle shaving of the hair over the center of their backs and they were randomly classified into four groups. Control group (I), 20 rats were divided into four subgroups (five animals each). Subgroup Ia, animals were left without treatment, Subgroup Ib, animals were injected subcutaneously with 1 ml of Phosphate Buffer Saline (PBS) at the shaved areas. Subgroup Ic, shaved areas were topically treated with growth factors gel after micro-needling procedure (Three topical treatments were repeated each one performed every 10 days). Subgroup Id, rats were subcutaneously injected with one dose of purified exosome concentrate containing 300 mg of total protein. Group (II)-(photoaged untreated group), five rats, each was exposed to UVA þ UVB irradiation for two weeks (five days per week) on the shaved areas using UV lamp. Group (III)-(photoaged exosome-treated group), five rats, each was exposed to UVA þ UVB irradiation similar to group II. The animals were injected with one dose of purified exosome concentrate containing 300 mg of total protein subcutaneously at the shaved areas. Group (IV)-(Photoaged and topically treated with growth factors), five rats each was exposed to UVA þ UVB irradiation similar to group II. Then, the animals were treated topically as in subgroup C. The back skin was dissected and processed to prepare sections for light microscopic examination with H&E, Masson's trichrome, Orcein and PAS stains. Immunostaining for KI67and CD31 were done. Morphometric and statistical analysis were performed. Results: Group II revealed significant decrease in the epidermal thickness, hair follicles were scanty and disorganized. Orcein sections showed short fragmented elastic fibers and irregular arrangement of collagen fibers with Masson's trichrome stain. KI67 positive cells was higher than other groups and CD31 was the opposite. Groups III and IV showed marked decrease in the previously mentioned microscopic changes denoting amelioration of the recorded photoaged epidermal and dermal changes. Conclusion: The current study concluded that both exosomes and topically applied Growth factors over three divided doses accompanied with micro-needling have resulted in a significant amelioration of the altered microscopic photoaging changes observed after exposure of the rat thin skin to the UV rays. Furthermore, the improvement was more obvious with the topically applied growth factors compared to one dose of exosomes concentrate. Further studies are recommended using repeated application of exosomes and also in combination with microneedling to stabilize the best protocol for treatment. [ABSTRACT FROM AUTHOR]