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Salidroside is considered as the one of the most critical constitutes needed and responsible for multiple therapeutic benefits of Rhodiola rosea L., including anti-aging, anti-inflammation, and anti-oxidative effects. Direct demonstration regarding the role of salidroside in anti-aging process is still deficient. In this study, we first investigated the toxicity of salidroside in human dermal fibroblasts and its permeation ability through nude mouse skin. Tropical application of salidroside was further evaluated on healthy human. Results showed salidroside significantly enhanced stratum corneum water content, skin smoothness, and skin elasticity .This study provides solid support that salidroside has anti-aging effect and may be useful in medical cosmetology.