Objective: To investigate the effects of rosiglitazone on hyperglycemia and insulin resistance (IR) in rats with cecal ligation and puncture (CLP) induced sepsis. Methods: Eighteen SD rats were equally randomized into sham operation group, sepsis group and rosiglitazone pretreatment plus sepsis group (rosiglitazone group). Sepsis in rats was induced by means of CLP, and rats in rosiglitazone group were treated with rosiglitazone (20 mg/kg) by gavage 30 min before CLP. The fasting plasma glucose (FPG) levels in rats were measured in tail-vein blood samples before and 30, 60, 90, 120 and 150 min after CLP. The rats were sacrificed at 150 min, the fasting insulin (FINs) levels were determined, and the homeostasis model assessment insulin resistance indexes (HOMA-IRI) were calculated. In addition, the TNF-α concentrations in rat serum and jejunal tissues were measured. Results: The FPG level in rats of sepsis group was significantly increased compared with the level before surgery, and the FPG levels at each time point were all significantly higher than those of sham operation group (all P<0.05), while the change in FPG level in rats of rosiglitazone group was not evident, and its FPG levels showed no statistical differences compared with sham operation group at each time point (all P>0.05). The FINs level and HOMA-IRI as well as the TNF-α concentrations in the serum and jejunal tissues in sepsis group were all significantly higher than those in sham operation group (all P<0.05), but these parameters in rosiglitazone group changed unremarkably and presented no statistical differences versus sham operation group (all P>0.05). Conclusion: Rosiglitazone pretreatment can improve the IR state, and also reduce the systemic inflammatory response in rats with CLP induced sepsis.