Etlingera rubroloba A.D Poulsen (E. rubroloba) plants from the genus Etlingera, empirically used as traditional medicine by several ethnicities in Southeast Sulawesi, namely to increase endurance and relieve joint pain. The purpose of this study was to determine the antihyperuricemia activity on uric acid levels and cyclooxygenase-2 (COX-2) levels in vivo in mice. This study used six groups of test animals consisting of normal, negative (Na-CMC) 0.5%, positive control (allopurinol) and dose groups of ethanol extract of E. rubroloba fruit 100, 200 and 300 mg/g bw. Modeling of hyperuricemia test animals is done by inducing potassium oxonate. Measurement of uric acid levels by lateral chromatography method and COX-2 levels by ELISA method. The results showed that ethanol extract of E. rubroloba fruit can reduce uric acid and COX-2 levels (p<0.05). The results of the correlation statistical test showed a positive correlation between uric acid levels and COX-2 levels, where the decrease in uric acid levels was directly proportional to the decrease in COX-2 levels. This research can be a reference in the development of traditional medicine, especially anti-hyperuricemia.