Abstract: Objective To observe the therapeutic effect and mechanism of volatile oil angelica(VOOA) on knee osteoarthritis(KOA) rabbits.Methods A total of 30 Japanese white rabbits, aged six months, were divided randomly into five groups(n=6): a Control group, a Sham group, a KOA group, a KOA+VOOA group, and a KOA+CMC group. Except for those in the Control and Sham groups, the rabbits in other groups were subject to anterior cruciate ligament transection(ACLT) on the fight knee for establishing a KOA model of rabbits. After successful modeling, rabbits in the KOA+VOOA and KOA+CMC groups were intragastrically administered with 0.2 ml/kg VOOA and 15 mg/kg CMC for 32 consecutive days, while those in other groups were given the volume of normal saline. After treatment, the rabbits were sacrificed for sampling. The cartilage and synovial tissue of each group were observed by the naked eyes. The morphological changes of the cartilage were observed by hematoxylin-eosin(H-E) and saffron solid green staining, and the Mankin score was evaluated. The changes of IL-1, IL-1β, TNF-α and TGF-β in the serum and joint fluid were detected by enzyme-linked immunosorbent assay(ELISA). The expression of p-MAPK and p-NF-κB protein and mRNA in the cartilage were detected by Western blot and RT-qPCR.Results Compared with the Control and Sham groups, the KOA group showed significant decreases in the Mankin score(P＜0.01), serious cartilage loss, remarkable increases in IL-1, IL-1β and TNF-α in the serum and articular fluid(all P＜0.01), without significant difference in TGF-β. The KOA group also presented significantly up-regulated levels of p-MAPK and p-NF-κB proteins and mRNA(P＜0.01). These changes were remarkably reversed by VOOA and CMC administration, and all evaluation parameters were statistically different from those in the KOA group.Conclusions VOOA can effectively protect the cartilage tissue of KOA rabbits, which may be related to blockage of the MAPK/NF-κB signaling pathway.