Aim To investigate the role of lipoprotein lipase ( LPL) activator NO-1886 on the mRNA expression of peroxisome proliferator-activated receptors (PPAR), LPL and tumor necrosis factor-α (TNF-α) in Guizhou minipigs fed with high-fat and high-sucrose. Methods Guizhou minipigs were randomized in to three groups: control group, high-fat high-sucrose group, high-fat high-sucrose and NO-1886 treated group (1% NO-1886 supplemented into the diet after 4 months). Reverse transcription-polymerase chain reaction (RT-PCR) analysis of PPAR, LPL and TNF-α RNA is extracted from frozen tissues, and reverse transcription-polymerase chain reaction (RT-PCR) is performed. Results The high-fat and high-sucrose diet increased the levels of mRNA expression of PPAR α in liver and muscle and the levels of mRNA expression of TNF-α in fat while decreased the levels of mRNA expression of fat PPAR α. NO-1886 improves the glucose metabolism probably through stimulating PPAR α and LPL expression. NO-1886 reduced the mRNA expression of fat TNF-α, decreased the mRNA expression of PPAR α in muscle and liver. Conclusions NO-1886 may stimulate PPAR γ and LPL expression, reduce the mRNA expression of TNF-α and PPAR α, which would account for an important role of NO-1886 in preventing atherosclerosis and lowing the blood sugar.