Objective: To discuss the effect of upper-middle-lower universal gout formula on renal fibrosis in rats with uric acid nephropathy (UAN) by regulating the MEK/ERK/Nrf2 pathway. Methods: Rats were randomly assigned into control group, UAN group, gout formula group, MEK inhibitor (PD98059) group, and gout formula+MEK activator (PMA) group. A UAN model was constructed by combining adenine and potassium oxonate. Fully automated biochemical analyzer was used to detect renal function indicators of rats. HE, Masson, and PAS staining were performed to detect the pathological damage of kidney tissue in each group. Immunohistochemistry was performed to detect the expression of fibrosis related proteins in the renal tissues of rats in each group. DHE staining and ELISA were used to detect oxidative stress indicators in renal tissue of rats in each group. In addition, Western blot was performed to detect the levels of MEK/ERK/Nrf2 pathway related indicators in the kidney tissues of rats in each group. Results: Compared with the control group, the UAN group showed clear upregulation of renal index, SUA, Scr, BUN levels, and renal tissue inflammatory infiltration, fibrosis area, PAS positive area, α-SMA, TGF-β1, Collagen I expression, ROS, MDA, p-MEK1/2/MEK1/2, p-ERK1/2/ERK1/2, while downregulation of SOD, HO-1, and Nrf2 (P<0.05). Compared with the UAN group, the gout formula group and PD98059 group showed clear downregulation of renal index, SUA, Scr, BUN levels, and renal tissue inflammatory infiltration, fibrosis area, PAS positive area, α-SMA, TGF-β1, Collagen I expression, ROS, MDA, p-MEK1/2/MEK1/2, p-ERK1/2/ERK1/2, while upregulation of SOD, HO-1, and Nrf2 (P<0.05). Compared with the gout formula group, the gout formula+PMA group showed clear upregulation of renal index, SUA, Scr, BUN levels, and renal tissue inflammatory infiltration, fibrosis area, PAS positive area, α-SMA, TGF-β1, Collagen I expression, ROS, MDA, p-MEK1/2/MEK1/2, p-ERK1/2/ERK1/2, while downregulation of SOD, HO-1, and Nrf2 (P<0.05). Conclusion: The upper-middle-lower universal gout formula clearly improves renal fibrosis and oxidative stress damage in UAN rats by inhibiting the MEK/ERK pathway and activating Nrf2.