Abstract: AIM: To observe the effects of different doses of tangzhixiao on insulin sensitivity in high fructose-fed rats and to explore its mechanism. METHODS: Insulin-resistant (IR) models established in male Sprague Dawley rats were randomly divided into three groups. Rats were given a high-fructose diet or high-fructose diet containing two doses of tangzhixiao. Fasting blood glucose (FBG), fasting insulin (FINS) and LP were measured after 4 weeks. The HOMA model was used to evaluate IR. RESULTS: In rats fed with high fructose, LP was positively related to FINS and HOMA-IR. FINS, LP and HOMA-IR of different doses of the tangzhixiao group decreased compared with those in the control group, but significant changes were found only in high-dose tangzhixiao group (all P<0.05). CONCLUSION: Tangzhixiao greatly prevents IR, possibly by decreasing leptin levels.