The aim of this study was to determine the effect of Jiang-Tang-Ke-Li (JTKL), a Chinese medicine used to treat diabetes mellitus, on insulin resistance and hypertension in fructose-fed rats (FFR). Six-week-old male Sprague-Dawley rats were fed either normal rat chow (control) or a fructose-rich chow (FFR) for 6 weeks. For the last 2 weeks of the 6-week period of either diet, the rats were treated by gavage with gum arabic solution as a vehicle (control or FFR) or JTKL (3.24 g/kg/day; FFR+JT), and then an euglycemic hyperinsulinemic glucose clamp technique was performed to estimate insulin sensitivity. Systolic blood pressure was measured each week of the 6-week period. At the end of the glucose clamp, the soleus and extensor digitorum longus (EDL) muscles were dissected out for determination of the role of tumor necrosis factor (TNF)-alpha by an ELISA assay. Systolic blood pressures in the FFR groups were significantly higher than that in the control group, although there was no effect on systolic blood pressure for the last 2 weeks of treatment with JTKL. The average rate of glucose infusion during the glucose clamp, as an index of insulin sensitivity (M value), was significantly lower in the FFR than in the control rats, and treatment with JTKL for 2 weeks significantly increased the M value to that of control. TNF-alpha levels were significantly higher in the soleus and EDL muscles of the FFR (480+/-46 and 570+/-45 pg/g wet tissue in the soleus and EDL muscles, respectively) than in those of the control rats (177+/-34 and 206+/-33 pg/g wet tissue in the soleus and EDL muscles, respectively; p<0.01). Treatment with JTKL for 2 weeks significantly lowered TNF-alpha levels to the control levels (189+/-22 and 239+/-92 pg/g wet tissue in the soleus and EDL muscles, respectively). The results suggest that the Chinese medicine JTKL improves insulin resistance and modulates TNF-alpha in the soleus and EDL muscles in hypertensive and insulin-resistant fructose-fed rats.