Abstract: Objective:This work was to study the effect of astaxanthin esters in alleviating insulin resistance in mice induced by high-fat and high-surcose diet(HFD). Method:The insulin-resistant mouse model was established by HFD. Male C57BL/6J mice were randomly divided into six groups:The normal group(low-fat and low-sugar diet),the model group(HFD),the solvent control group,natural astaxanthin from Haematococcus pluvialis group,astaxanthin butyrate diester group,and astaxanthin stearate diester group. After 60 d of continuous gavage with astaxanthin esters(50 mg/(kg·bw)),fasting blood glucose,glucose tolerance,serum insulin level,serum lipopolysaccharide(LPS)level,bioaccessibility and the concentration of fecal short chain fatty acids(SCFAs)were measured. The morphology of the small intestine was observed. Result:Astaxanthin butyrate diester significantly reduced serum insulin and LPS levels in insulin-resistant mice(P<0.05),and improved glucose tolerance and insulin resistance(P<0.01). The histological morphology of small intestine was improved in astaxanthin butyrate diester group. The villus length and the ratio of villus length to crypt depth were significantly increased(P<0.05). The concentration of SCFAs in feces was significantly increased with astaxanthin butyrate diester. Conclusion:Astaxanthin butyrate diester had a better effect in improving insulin resistance than natural astaxanthin and astaxanthin stearate diester in mice induced by HFD. This might be due to the effects of the astaxanthin butyrate diester on intestinal barrier function,and gut microbial products LPS and SCFAs.