Objective:To evaluate the effects of cellulift ? administered intradermally by mesotherapy on collagen synthesis in D-galactose induced aging model of rats. Methods:The study was conducted between April and October in 2014 in the Department of Anatomy, Qindao University. 30 male rats were randomly allocated to three groups: aging treatment group, aging control group and normal group; each group had ten rats. Aging treatment group and the control group were subcutaneously injected with D-galactose prepared in saline 125 mg·kg -1·d -1 for 42 day. Normal group was injected with saline for 42 d with same method and dose. From the 18th day after shaving their hair, the dermis of two sides hip skin marked zone of aging treatment group were injected cellulift at a dose of 1 ml per week for 4 weeks. Meanwhile, the aging control group was administrated the same volume of saline with same method. In vivo skin collagen alterations were investigated by reflectance confocal microscopy 3 days after every treatment. Skin specimens were obtained in 42 days. In order to measure the dermal collagen density and dermal thickness, HE and Masson trichrome staining were performed, respectively. Immunohistochemical staining for TGFβ1 and proliferating cell nuclear antigen (PCNA) was performed. Also, the level of TGFβ1, Smad3, types Ⅰ and Ⅲ pro-collagen mRNA expression was assessed by real-time quantitative polymerase chain reaction. Results:As revealed by RCM, collagen density of aging treatment group increased gradually after treatments, while in aging control group it decreased with time. Measurement of dermal thickness, hydroxyproline content and TGFβ-1 mRNA and protein expression in treatment group increased significantly as compared with that in aging control group, but were significantly lower than that in normal group (F values were 25.45, 98.90, 37.94 and 21.35, respectively; P<0.05). Measurement of dermal collagen density, the mRNA expression of type I pre-collagen and Smad3 elevated over that of aging control group with significant difference (F values were 44.46, 29.54 and 10.01, respectively; P<0.05), and there was no difference between normal and aging treatment group ( P>0.05). The difference of PCNA expression between aging control and treatment groups was not significant ( P>0.05), and both were lower than normal group ( P<0.05) . Conclusions:Cellulift ? shows anti-aging effects by activating collagen synthesis and eventually causing dermal thickening. This effect is probably mediated by TGF-β1/Smad3 signaling pathway.