Scope: Conjugated linoleic acid (CLA), a bioactive substance predominantly found in ruminant products, improves insulin resistance and exhibits anti-inflammatory activity. The chief objective of the study is to investigate the effects and potential mechanisms of CLA on high fructose-induced hyperuricemia and renal inflammation. Methods and results: Hyperuricemia and renal inflammation are induced in rats by 10% fructose. Hyperuricemia, insulin resistance, and renal inflammation are evaluated. CLA potently ameliorates fructose-induced hyperuricemia with insulin resistance and significantly reduces the levels of inflammation factors in serum and kidney. It reverses fructose-induced upregulation of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) in the kidney. Moreover, CLA dramatically inhibits the activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. Additionally, CLA suppresses toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling activation to inhibit nuclear factor-kB (NF-kB) signaling in the kidney of fructose-fed rats. Conclusion: CLA ameliorates hyperuricemia along with insulin resistance and renal inflammatory, which may be associated with the suppression of renal GLUT9 and URAT1 in fructose-fed rats. Its molecular mechanism may be related to the inhibition of NLRP3 inflammasome and TLR4/MyD88 signaling pathway. Therefore, CLA may be a promising candidate for preventing fructose-induced hyperuricemia and renal inflammation.