P21Waf1/Cip1 is a potent cyclin-dependent kinase inhibitor. As a downstream mediator of p53, p21Waf1/cip1involves in cell cycle arrest, differentiation and apoptosis. Previous studies in human cells provided evidencefor a link between p21Waf1/cip1 and cellular senescence. While in murine cells, the role of p21Waf1/Cip1is indefinite. We explored this issue using NIH3T3 cells with inducible p21Waf1/cip1 expression. Induc-tion of p21Waf1/Cip1 triggered G1 growth arrest, and NIH3T3-p21 cells exhibited morphologic features,such as enlarged and flattened cellular shape, specific to the senescence phenotype. We also showed thatp21Waf1/Cip1-transduced NIH3T3 cells expressedβ-galactosidase activity at pH 6.0, which is known to bea marker of senescence. Our results suggest that p21Waf1/cipx can also induce senescence-like changes inmurine cells.