The effects of curcumin on mast cell chymase activity in fatty liver and serum fetuin-A levels in rats fed a high-fat diet (HFD) were investigated. Male Sprague-Dawley rats received HFD (60% of total calories from fat) and 1 g curcumin/kg HFD for 16 weeks. Hepatic chymase activity was determined using spectrophotometric analysis while liver lipid levels were measured using colorimetric methods and serum fetuin-A, insulin, leptin, and adiponectin levels were detected using commercial enzyme-linked immunosorbent assay kits. Hepatic fat accumulation and fibrotic changes were ameliorated with curcumin treatment. Curcumin significantly reduced hepatic lipids, chymase activity, and serum fetuin-A levels. Decreased serum leptin and augmented adiponectin levels were also observed. These findings suggest that curcumin attenuated hepatic fat accumulation and regulated adipokine levels. The reduction of liver chymase activity and serum fetuin-A levels may also contribute to the beneficial effects of curcumin in fatty liver disease induced inflammatory status.