Wogonoside is a natural flavonoid isolated from Scutellaria baicalensis Georgi. The effect of wogonoside on myocardial remodeling in infarction rats and the possible mechanisms involved were investigated. Our results showed that compared with control Wistar rats, systolic blood pressure (SBP) level of model group rats was significantly increased (P < 0.01). Compared with model group, SBP levels of middle, high dose wogonoside and benazepril treated groups were significantly decreased (P < 0.01), while low dose wogonoside treated group showed no SBP decrease effect (P < 0.01). Wogonoside treatment could significantly decrease the myocardial hydroxyproline level (P < 0.01), indicating that the collagen cardiac muscles deposition was reduced. Moreover, we found that NF-kappa B DNA binding activity was dramatically decreased after treated with wogonoside for 6 h. Wogonoside also induced the dephosphorylation and up regulation of I kappa B-alpha. All above results suggest that wogonoside exerts an inhibitory effect on myocardial fibrosis, which may be related to decreasing blood pressure, reducing the myocardial collagen deposition.