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Backgroud Angiotensin Ⅱ (Ang Ⅱ), a principal effector of renin-angiotensin system (RAS) and increased in aging tissues, can stimulate JAK/STAT pathway via the G-protein-coupled Ang Ⅱ receptor type Ⅰ (AT1) and induce nuclear translocation of signal transducers and activators of transcription (STAT). To further explore the role of Ang Ⅱ in aging, we examined the effect of Ang Ⅱ on human replicative senescent diploid fibroblast WI-38cells.Methods Human senescent WI-38 cells were incubated with Ang Ⅱ, receptor antagonist PD123319, valsartan,STAT3 sense plasmid, and/or STAT3 antisense plasmids. Methods were applied including electrophoretic mobility shift assay (EMSA), West blot, transfection, and laser scanning confocal microscopy.Results It was found that cultured human senescent WI-38 cells constitutively expressed tissue inhibitor of metalloproteinase-1 (TIMP-1), and Ang Ⅱ induced TIMP-1 protein expression in both time- and dose-dependent manners. Ang Ⅱ induced STAT-DNA binding activity also in both time- and dose-dependent manners. And supershift assay showed that the sis-inducing factor (SIF) band contained STAT3 proteins. STAT3 antisense oligonucleotides could inhibit both Ang Ⅱ-induced STAT3-DNA binding activity as well as TIMP- 1 expression.Conclusion Ang Ⅱ could up-regulate TIMP-1 expression through activating STAT3 signal pathway in human senescent cells, indicating that Ang Ⅱ-STAT3-TIMP-1 pathway may be involved in the mechanism of sclerosis in aging tissues.