Introduction: One of the most frequent types of arthritis is osteoarthritis, also referred to as a degenerative joint disease. Interleukin-1β (IL-1β) and nitric oxide (NO) are essential factors in the pain response; IL-1β and NO are responsible for increasing the production of matrix metalloproteinases (MMP) and a disintegrin-like and metalloproteinases with thrombospondin motifs (ADAMS) in chondrocytes. Arcangelisia flava (L.) Merr. Has been traditionally used to treat jaundice, liver disease, diarrhea, fever, and inflammation., Methods: This study used in vitro and in vivo models to determine the effect of a 70 % ethanol extract of Arcangelisia flava (L.) Merr. stems on the inhibition of NO production in RAW 264.7 cells induced with lipopolysaccharide (LPS) and IL-1β in osteoarthritis rats induced with monosodium iodoacetate (MIA). The NO inhibition test was determined by the NO colorimetric assay using Griess reagent and measured by the ELISA plate reader. The measurement of joint diameter and hyperalgesia in osteoarthritis rats was carried out once a week for 7 weeks, and then the IL-1β levels were measured at weeks 3 and 7., Result: The viability of cell line this extract was greater than 80 %, and the extract at 25, 50, and 100 μg/mL significantly inhibited NO production ( p < 0.0001) in RAW 264.7 cells induced with LPS. Meanwhile, this extract at 10, 30, and 90 mg/200g BW increased latency time, reduced joint swelling, and reduced IL-1β levels in the serum in the osteoarthritis rat model., Conclusion: 70 % ethanol extract of Arcangelisia flava (L.) Merr. Has the potential to be an anti-osteoarthritis drug., Competing Interests: The authors declare that they have no conflicts of interest related to the publication of this study. The authors whose names are listed immediately below certify that they have NO affiliations with or involvementin any organization or entity with any financial interest (Such as honoraria; educational grants; participations in speakers' bureaus; membership, employment consultancues, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (Such as personal or proffesional relationship, affiliation, knowledge or benefits) in the subject matter or materials discussed in this manuscript. This statement is signed by all the authors to indicate agreement that the above information is true and correct., (© 2024 The Authors.)