Abstract: [Abstract] Objective To investigate change of TLR4 in OLETF rats with insulin resistance(IR), and study the effect of peroxisome proliferator-activated receptor γ（PPAR-γ）pioglitazone (PIO) on the expression of TLR4, and the possible mechanisms of the PIO reducing the risk of cardiovascular diseases. Methods: 24 OLETF rats were fed with high-fat diet for 20 weeks to establish the IR model. 24 OLETF rats with IR were randomly assigned into two groups: the model group (group M), in which the rats were fed with high-fat diet; the PIO group (group P), in which the rats were fed with high-fat diet and PIO. 12 LETO rats fed with normal diet were served as normal control group (group NC). After 20 weeks of drug intervention, the plasma levels of FINS, FBG, blood lipid, IL-18 and TLR4 were detected in every group. Results Comparing with group NC, the FBG, Blood lipid, IL-18 and TLR4 were significantly increased in group M（P<0.05 or P<0.01）; comparing with group M, the FBG, Blood lipid were improved in group P, and The serum IL-18,TLR4 were significantly lower in the group P than that of group M（P<0.05 or P<0.01）. Conclusion TLR4 may be involved in IR by promoting inflammatory response, and PIO can significantly improve IR and inflammatory stage, and reduce the risk of cardiovascular diseases by inhibiting the expression of TLR4.

Key words: insulin resistance, interleukin-18, toll-like receptor 4, cardiovascular diseases, rats, inbred OLETF, pioglitazone