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Sodium tanshinone IIA sulfonate (STS), a derivative of tanshinone IIA, is isolated from the root of Salvia miltiorrhiza known as “Danshen”. Although injection of S. miltiorrhiza extract and STS is used successfully in clinics in China for treating postmenopausal syndrome, the exact mechanism for its therapeutic basis is poorly understood. The present study was undertaken to characterize the effect of STS on the expression of prolactin releasing peptide (PrRP) in the medulla oblongata in ovariectomized rats. In addition, estrogen (E2) levels were detected in OVX rats treated with STS. The results showed that STS might significantly increase the blood level of E2 and PrRP cell number in the medulla oblongata of ovariectomized rats. The number of PrRP immunoreactivity (ir) neurons was higher in the group ovariectomized with STS than that in the ovariectomized group. The numbers of PrRP-ir neurons in Sham and Sham + STS were not significantly different between the two groups. These results suggest that the mechanism that STS improved postmenopausal symptoms induced by ovariectomy in rats might be related to the modulation of the blood E2 level and the expression of PrRP in medulla oblongata of ovariectomized rats.