Abstract: Objective To observe the effect of medium-chain fatty acid（MCFA） on high-density-lipoprotein（HDL） in serum,liver and small intestine of C57BL/6J mice fed with high fat diet. Methods Thirty-six male C57BL/6J mice,fed with high fat diet,were randomly divided into 2mg/kg MCFA group,4mg/kg MCFA group and 4mg/kg long-chain fatty acid（LCFA） group,12 in each group.After the mice received intra-gastric fat acids（once a day for 2 weeks）,they were killed.Their body,fat pad,and liver were weighed.Their HDL and apolipoproteinA1（ApoA1） levels in serum,liver,small intestine were measured by ELISA.Expression of HDL and ApoA1 mRNA in liver and small intestine was detected by real-time-PCR. Results The liver weight was significantly lower,while the serum HDL-C/LDL-C ratio and the expression level of HDL mRNA and ApoA1 mRNA in liver and small intestine were significantly higher in 2mg/kg MCFA group than in 4mg/kg LCFA group（P＜0.05）.The serum HDL-C and HDL levels,and the expression level of HDL mRNA in liver and small intestine were significantly higher in 4mg/kg MCFA group than in LCFA group（P＜0.05）.The expression of HDL mRNA and ApoA1 mRNA in liver and small intestine was significantly different between 2mg/kg and 4mg/kg MCFA groups（P＜0.05）. Conclusion MCFA can elevate the HDL level in serum,liver and small intestine,up-regulate the expression of HDL mRNA but not the expression of ApoA1 mRNA in liver and small intestine of C57BL/6J mice fed with high fat diet.