Objective To explore possible mechanism of the effect of pioglitazone and the relation between pioglitazone and postmenopausal osteoporosis by observing the effect of pioglitazone on body weight, blood lipid, FNS, HOMA-IR, E2, BMD, BALP, PPARγ2, IL-1β, IL-6, and TNF-α in ovariectomized rats. Methods One hundred and forty-four 3-month-old healthy female Wistar rats were divided into Sham-ovariectomized group and ovariectomized group. Rats in two groups were given normal saline, pioglitazone 4 mg/kg.d or pioglitazone 20 mg/kg.d respectively. On 0, 4, 8, and 12 weeks 6 rats from each group were randomly selected to measure relevant biochemical indicators. Bone mass of the animals was detected using duel-energy X-ray absorptiometry. PPARγ2 was examined using RT-PCR. IL-1β, IL-6, TNF-α, and BALP were measured using ELISA method. Results 1) Body weight, TG, CHO, LDL-C, FNS, HOMA-IR, PPARγ2, IL-1β, IL–6, TNF-α, and BALP increased, and E2, HDL-C, and BMD decreased in ovariectomized group, compared to another group. The difference was statistically significant (P<0.01). 2) With different doses of pioglitazone treatment in ovariectomized group, HOMA-IR decreased dose-dependently (P<0.01), PPARγ2 increased time- and dose-dependently (P<0.05), and IL-1β, IL-6, TNF-α, and BALP decreased time- and dose-dependently (P<0.05). The correlation analysis showed that PPARγ2 negatively correlated with IL-1β, IL-6 and TNF-α (-0.5 |