Abstract: Objective To study the effect of Shaoyangzhugu (SYZG) Formula (a formula consisting of 9 traditional Chinese drugs) in delaying the degeneration of articular cartilage and the role p19Arf-p53-p21Cip1 signaling pathway in mediating this effect. Method Thirteen aged cynomolgus monkeys with degenerative knee joints were selected based on X-ray findings, and one of them was randomly selected for pathological observation. The other monkeys were randomized equally into SYZG Formula group (treated with SYZG decoction), ammonia moxime group and saline group. All the monkeys were sacrificed after 8 weeks of treatment with intragastric administration of the drugs or saline. The pathology in the knee joint articular cartilage was observed and the mRNA and protein expressions of p19Arf, p53, and p21Cip1 in the articular cartilage were detected using RT-qPCR and Western blotting. Results The pathological findings of the articular cartilage in old cynomolgus monkeys were consistent with the characteristics of knee osteoarthritis (KOA). Mankin scores of the cynomolgus monkeys were 7.38±0.52 in SYZG Formula group, 7.88±0.83 in ammonia moxime group, and 8.38±0.74 in saline group, showing a significant difference between SYZG Formula group and saline group (P<0.05). The expressions of p19Arf, p53, and p21Cip1 were the lowest in SYZG Formula group and the highest in saline group with significant differences among the 3 groups (P<0.05). Conclusion SYZG Formula can delay chondrocyte senescence by regulating p19Arf- p53- p21Cip1 signaling pathway to delay articular cartilage degeneration in aged cynomolgus monkeys.