Ethnopharmacological relevance: Periploca forrestii Schltr. is a classical traditional Chinese medicine (TCM) called Heilonggu (HLG) in China. According to the theory of TCM, it possesses the efficacy of eliminating wind and removing dampness. In clinical practice, it is commonly used for the treatment of rheumatoid arthritis. The present work aimed to evaluate the anti-rheumatism activity of HLG ethanol extract and reveal the underlying molecular mechanism by employing an animal model of collagen-induced rheumatoid arthritis (CIA) in rats. Materials and methods: The CIA was induced in male Sprague Dawley rats by intradermal injection of bovine collagen-II in complete Freund's adjuvant (CFA) at the base of tail. The rats received oral administration of HLG (200 and 400 mg/kg) from day 1, with the treatment lasting for 28 days. A variety of indicators were measured for evaluation of anti-rheumatism effect, including paw swelling, arthritis scores, and histopathological changes. Furthermore, the serum levels of tumor necrosis factor-alpha (TNF-alpha), interleuldn-6 (IL-6), and prostaglandin E2 (PGE2), as well as cyclooxygenase-2 (COX-2), nuclear factor NF-kappa B p65 and Src kinase in joint synovial tissues were detected to explore the possible mechanisms. Results: The administration of HLG significantly restored type II collagen-induced arthritis in rats as evidenced by decrease in paw swelling and inflammatory factors in serum. Meanwhile, this treatment also notably reduced NF-kappa B p65 and COX-2 expression. Surprisingly, the activity of Src kinase was also inhibited demonstrated by downregulation of phosphorylated Src. Conclusion: Our results revealed that HLG possessed observable therapeutic action on collagen-induced arthritis by inhibiting the activation of Src and nuclear translocation of NF-kappa B in rats. HLG may serve as a potential candidate for the management of patients with RA.