BACKGROUND AND OBJECTIVE: CEFFE (Cell-free fat extract) treatment for periocular fine lines requires thorough clinical evaluation to determine its efficacy and safety in enhancing skin quality. The research enrolled 10 healthy female participants aged 31-58, focusing on skin texture, elasticity, and barrier function. METHODS AND RESULTS: CEFFE treatment demonstrated significant benefits, with notable improvements observed as early as 3 months posttreatment, which continued throughout the 12-month follow-up period. Objective assessments revealed reductions in SEr% and SEw%, indicative of reduced skin roughness and wrinkles, particularly pronounced after the third month of treatment. Enhanced skin elasticity, as indicated by improvements in R2%, R5%, and R7%, was observed, with the most significant enhancements noted at the 6-month follow-up. Furthermore, TEWL decreased consistently, highlighting CEFFE's potential in maintaining the skin's barrier function and moisture retention. High patient satisfaction levels, with 70% expressing satisfaction ranging from satisfied to very satisfied, underscored CEFFE's clinical significance. CONCLUSIONS: CEFFE demonstrates potential as an effective and safe intervention for addressing periocular fine lines, providing a solution for fine lines while ensuring skin health (ChiCTR1900024329).