The aim of the present experiment was to study the effects of metformin (MF) on serum concentrations of sex hormone, leptin and insulin in ovariectomized (OVX) Sprague-Dawley (SD) rats. The serum estradiol (E2), progesterone (P), leptin and insulin concentrations were measured with radioimmunoassay (RIA). Compared with SHAM operated rats, the serum concentrations of E2 and P were significantly lower (P < 0.01), but leptin and insulin were significantly higher in OVX rats (P < 0.01). MF (135mg kg(-1) d(-1), ig, 30 d) had no evident effects on serum concentrations of E2, P, leptin and insulin in OVX rats. MF (270 mg kg(-1) d(-1), ig, 30 d) markedly increased serum concentrations of E2 and P (P < 0.05) while decreased serum concentrations of leptin and insulin (P < 0.05 and P < 0.01) in OVX rats. We concluded that long-term treatment of high dose MF cannot only significantly decrease serum concentrations of leptin and insulin, but also increase E2 and P in OVX SD rats.