Objective To establish a mouse model of acute gouty arthritis (AGA), and to study whether oltipraz can improve the joint inflammation and pain in this model. Methods Healthy male C57 / BL6 mice were randomly divided into control, MSU+Vehicle (MSU+Veh), MSU+Oltipraz high-dose (MSU+100 mg / kg oltipraz), MSU+Oltipraz low-dose (MSU+30 mg / kg oltipraz), and MSU+Indomethacin (MSU+Indo) groups. Mice of the control group were injected with phosphate buffered saline, whereas the other groups were injected with monosodium urate (MSU) in the right ankle to establish AGA. After the establishment of AGA, the MSU+Oltipraz group was intraperitoneally injected with oltipraz, the MSU+Indo group was intraperitoneally injected with indomethacin at the same time point, and mice in the other groups were intraperitoneally injected with the same volume of vehicle. Calipers were used to measure ankle joint swelling before and after model establishment and treatments. The 50% mechanical paw withdrawal threshold ( 50% PWT) of mice was measured by the von Frey method . Pathological changes of ankle synovial tissues were evaluated. The DigiGait imaging system was used to measure the gait of mice and changes of gait behavior before and after model establishment. An oxidative molecular detection kit was used to detect the oxidative stress-related molecules in mouse ankle joints. The expression levels of inflammatory factors in ankle joints were examined by qPCR. Results Compared with the control group, the MSU group had obvious ankle joint swelling and the 50% PWT was significantly reduced (P<0. 01). Pathological analysis indicated that the synovial tissues of the ankle joint showed extensive inflammatory cell infiltration in the MSU group compared with the control group (P<0. 05). Gait analysis showed that the stride length of hind limb was significantly shortened, and the paw area was significantly reduced (P<0. 01) in the MSU group compared with the control group. Compared with the MSU +Veh group, the 50% PWT of the ipsilateral side of mice in the MSU+100 mg / kg oltipraz group was significantly increased (P<0. 01), the ankle joint swelling was greatly reduced and gait parameters were markedly improved (P<0. 05), the level of oxidative stress in ankle joints was significantly decreased (P<0. 05), and the expression levels of inflammatory cytokine IL-1β and TNF-α mRNAs were dramatically decreased in the MSU+100 mg / kg oltipraz group compared with the MSU+Veh group ( P< 0. 01), an effect similar to that of indomethacin, whereas 30 mg / kg oltipraz had no significant effect. Conclusions Oltipraz can alleviate ankle joint swelling and mechanical hyperalgesia in the AGA mouse model. This therapeutic effect is probably related to reduced oxidative stress and inflammatory cytokine levels, and the increased expression of antioxidant substances in the ankle tissue of AGA mice by oltipraz treatment.