The leaves of Mangifera indica L. (Anacardiaceae) is used as a medicinal material in traditional herb medicine for a long time in India, China, and other Eastern Asian countries. Our present study investigated the therapeutic effects of the ethanol extract from Mangifera indica (EMI) in rat with monosodium urate (MSU) crystals-induced gouty arthritis. Effects of EMI (50, 100, and 200 mg/kg, p.o.) administrated for 9 days on the ankle swelling, synovial tumor necrosis factor-alpha (TNF-α), and interleukin-1beta (IL-1β) levels were assessed in MSU crystal rat. Data from our study showed that rat with gouty arthritis induced by MSU crystal demonstrated an elevation in ankle swelling, synovial TNF-α, IL-1β mRNA, and protein levels. Oral administration of 100 and 200 mg/kg EMI for 9 days reversed the abnormalities in ankle swelling, synovial TNF-α, IL-1β mRNA, and protein levels. The results indicated that the beneficial antigouty arthritis effect of EMI may be mediated, at least in part, by inhibiting TNF-α and IL-1β expression in the synovial tissues. Our study suggests that Mangifera indica and its extract may have a considerable potential for development as an anti-gouty arthritis agent for clinical application.