Abstract: OBJECTIVE To investigate the improvement effect and mechanism of metformin(MF) on insulin resistance in castrated female rats. METHODS The levels of serum estradiol(E₂), progesterone (P) and insulin (INS) were determined by radioimmunoassay method. Tumor necrosis factor-a (TNF-α) level was measured by enzyme-linked immunosorbent assay. Gene expression of pancreas islet suppressor of cytokine sighting-3(SOCS-3) was determined by using reverse transcriptase polymerase chain reaction. RESULTS Compared with NS group, the serum E₂ and P content in OVX group were significantly decreased, the TNF-α, INS content were significantly increased , while the SOCS-3 mRNA expression of pancreas islets were significantly increased(P<0.01). Compared with the OVX group, MF low group has no significant change. Serum E₂ and P content were significantly increased (P<0.05) in MF high group. The TNF-α, INS content significantly decreased (P<0.05 or P<0.01), while the SOCS-3 mRNA expression of islets were significantly decreased (P<0.01). CONCLUSION Long-term with a large dose of MF 270 mg·kg^-1·d^-1can improve ovariectormized rats insulin resistance phenomenon. The mechanism may be related with the decreased of TNF-α and SOCS-3 mRNA expression of islets.