Artesunate (ART) is a semi-synthetic derivative of artemisinin and used preferentially in treatment of malaria in China. ART has strong anti-inflammatory, anti-tumor, and anti-angiogenic properties. Although the pharmacological effect of ART in osteoarthritis (OA) is unknown, evidence suggests that ART might regulate osteoclastogenesis through NF-κB signaling. In this study we explored the therapeutic effect of ART in an anterior cruciate ligament transection (ACLT)-induced OA model. We found that ART effectively relieved ACLT-induced osteoarthritis, as demonstrated by the improvement expression of pathological genes. We further demonstrated that ART markedly reduced OA-associated osteoclastogenesis and angiogenesis. In addition, ART also regulated inflammatory response and inhibited the activation of Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) signaling in ACLT rats. Taken together our study has identified a novel function of ART and provided a molecular basis for ART potential applications in the treatment of OA and other joint disorders.