〔Abstract〕 Objective To investigate the role of KAT7 in cartilage cell and tissue ageing by establishing an over-replicating-induced primary mouse cartilage cell ageing model and a mouse natural ageing model. Methods Chondrocytes of the mouse knee joint were obtained by type II collagenase digestion and identified by toluidine blue staining and Col II staining. The age-related proteins and KAT7 expression levels in cartilage cells from different generations of mice were discovered using Western blot and cellular immunofluorescence techniques, and the aging of the cells was assessed by SA-β-Gal coloring. The pathological alterations were examined in the joints of 22-month-old mice compared to 2-month-old mice using HE staining and safranin O-solid green staining. Additionally, immunohistochemical analysis was done to observe the expression of KAT7 and p53 in mouse joint tissue. Results Compared with the control group, the expression levels of KAT7 protein and p21 and p53 in aged mouse chondrocytes significantly increased. WM-3835, a commonly inhibitor of KAT7 that possess the capacity on halting the protein expression procedure of gene KAT7 as well as p21 in ageing chondrocytes. SA-β-Gal staining showed a significant increase in positive staining of chondrocytes in the eighth generation(P8) compared to the first generation(P1). Compared with the cartilage tissue of young mice, the cartilage tissue of elderly mice presents a near-bone distribution, with a decrease in cartilage surface integrity, a significant increase in the number of hypertrophic chondrocytes, and more KAT7 and p53 cells that were positive. Conclusion The expression of KAT7 increases in the ageing chondrocytes and the cartilage tissue of ageing mice, reveales the potential significance of KAT7 correlated to cellular aging process in cartilage.