Abstract: Objective To establish a IL-1β-induced rat chondrocyte inflammatory response model, and investigate the effects of catalpol (CAT) on cartilage degeneration of rats with osteoarthritis (OA). Methods To investigate the role of CAT in osteoarthritis and its specific mechanism, chondrocytes from 12 SD rats were randomly selected for primary culture. Chondrocytes were divided into four groups: control group, IL-1β group, IL-1β+CAT 10 μg/mL group and IL-1β+CAT 50 μg/mL group. In animal experiments, 12 rats were randomly divided into three groups: Sham group, OA group and OA+CAT group, with 4 rats in each group. OA group underwent right anterior cruciate ligament transection and meniscectomy. The experimental group, namely OA+CAT group, was given intraperitoneal injection of CAT [5 mg/(kg·d)] after resection of right anterior cruciate ligament transection and meniscus. Catabolic metabolism, apoptotic level and relative signaling pathway were measured by Western blotting, RT-PCR and immunofluorescence staining. We also assess the cartilage degeneration in an experimental rat model using Safranin O/fast green staining and Osteoarthritis Research Society International (OARSI) system. Results ①CAT prevented chondrocyte apoptotic level triggered by IL-1β; ②CAT suppressed the release of catabolic enzymes, and inhibited the degradation of extracellular matrix induced by IL-1β; ③CAT inhibited the nuclear factor Kappa B pathway, reduced the production of inflammatory cytokines (IL-6, TNF-α) in IL-1β-treated chondrocytes; ④CAT partially reversed cartilage degeneration in the knee joint in animal model of OA. Conclusion CAT treatment can attenuate IL-1β-induced inflammatory response and catabolism in rat chondrocytes by inhibiting the NF-κB pathway, suggesting the therapeutic potential of CAT for the treatment of OA.