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Photoaging is generally treated by ablative procedures that injure the epidermis and basal membrane and lead to fibrosis of the papillary dermis. Damaging the epidermis significantly can cause potential adverse effects such as dyspigmentation. It was recently shown in clinical trials that percutaneous collagen induction therapy is an alternative for safely treating wrinkles and scars and for smoothening the skin without the risk of dyspigmentation.The purpose of this study was to increase current knowledge regarding whether percutaneous collagen induction therapy presents an effective means for skin rejuvenation without risk of dyspigmentation, as the authors' clinical data suggested. Fifty-six rats were assigned to three groups: group A (n = 24), percutaneous collagen induction therapy plus skin care; group B (n = 24), skin care; and group C (n = 8) controls. The authors evaluated the effect of percutaneous collagen induction therapy on the epidermis, melanocytes, and the pigmentation markers interleukin-10 and melanocyte-stimulating hormone.Percutaneous collagen induction therapy left the epidermis intact without any damage to the stratum corneum, any other layers of the epidermis, or the basal membrane. No signs of dermabrasive reduction of epidermal thickness were evident 24 hours after the procedure. The number of melanocytes neither increased nor decreased in any of the groups. DNA microarray experiments demonstrated that interleukin-10 was increased in percutaneous collagen induction therapy–treated skin after 2 weeks. Concerning the MC1R (melanocyte-stimulating hormone) gene, gene expression microarray analysis indicated a faint down-regulation both 24 hours and 2 weeks after percutaneous collagen induction therapy.Percutaneous collagen induction therapy offers a modality with which to rejuvenate and improve skin appearance and quality without risk of dyspigmentation.