The present study investigated the action of copaiba oil (Copaifera reticulata) on the systemic inflammation, oxidative status, and liver cell metabolism of rats with adjuvant-induced arthritis. The later is an experimental autoimmune pathology that shares many features with the human rheumatoid arthritis. Holtzman rats were distributed into the following groups: control (healthy) rats; control rats treated with copaiba oil at the doses of 0.58 and 1.15 g · kg , arthritic rats, and arthritic rats treated with copaiba oil (0.58 and 1.15 g · kg ). The oil was administrated orally once a day during 18 days after arthritis induction. Both doses of copaiba oil improved the paw edema and the dose of 0.58 mg · kg improved the swollen adrenals and lymph nodes besides decreasing the plasmatic myeloperoxidase activity (-30%) of arthritic rats. Copaiba oil (1.15 g · kg ) abolished the increases of protein carbonyl groups and reactive oxygen species in the liver and both doses increased the liver GSH content and the catalase activity in arthritic rats. Copaiba oil (1.15 g · kg ) decreased glycolysis (-65%), glycogenolysis (-58%), and gluconeogenesis (-30%) in the liver of arthritic animals. However, gluconeogenesis was also diminished by the treatment of control rats, which presented lower body weight gain (-45%) and diminished number of hepatocytes per liver area (-20%) associated to higher liver weight (+29%) and increased hepatocyte area (+13%). The results reveal that copaiba oil presented systemic anti-inflammatory and antioxidant actions in arthritic rats. These beneficial effects, however, were counterbalanced by harmful modifications in the liver cell metabolism and morphology of healthy control rats. J. Cell. Biochem. 118: 3409-3423, 2017. © 2017 Wiley Periodicals, Inc.